Vern L Schramm

Summary

Affiliation: Albert Einstein College of Medicine
Country: USA

Publications

  1. pmc Plasmodium falciparum parasites are killed by a transition state analogue of purine nucleoside phosphorylase in a primate animal model
    Maria B Cassera
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, United State of America
    PLoS ONE 6:e26916. 2011
  2. pmc Immucillin-H, a purine nucleoside phosphorylase transition state analog, causes non-lethal attenuation of growth in Staphylococcus aureus
    Christopher F Stratton
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461
    Bioinformation 9:9-17. 2013
  3. pmc Transition States, analogues, and drug development
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx New York 10461, United States
    ACS Chem Biol 8:71-81. 2013
  4. doi request reprint Enzymatic transition states, transition-state analogs, dynamics, thermodynamics, and lifetimes
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Annu Rev Biochem 80:703-32. 2011
  5. ncbi request reprint Energetic mapping of transition state analogue interactions with human and Plasmodium falciparum purine nucleoside phosphorylases
    Andrzej Lewandowicz
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 280:30320-8. 2005
  6. pmc Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases
    Yong Zhang
    From the Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 and
    J Biol Chem 288:34746-54. 2013
  7. doi request reprint Tryptophan-free human PNP reveals catalytic site interactions
    Mahmoud Ghanem
    Departments of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 47:3202-15. 2008
  8. pmc Structure and inhibition of a quorum sensing target from Streptococcus pneumoniae
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 45:12929-41. 2006
  9. ncbi request reprint Over-the-barrier transition state analogues and crystal structure with Mycobacterium tuberculosis purine nucleoside phosphorylase
    Andrzej Lewandowicz
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 42:6057-66. 2003
  10. ncbi request reprint Assignment of downfield proton resonances in purine nucleoside phosphorylase immucillin-H complex by saturation-transferred NOEs
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 43:1980-7. 2004

Collaborators

Detail Information

Publications90

  1. pmc Plasmodium falciparum parasites are killed by a transition state analogue of purine nucleoside phosphorylase in a primate animal model
    Maria B Cassera
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, United State of America
    PLoS ONE 6:e26916. 2011
    ..The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent...
  2. pmc Immucillin-H, a purine nucleoside phosphorylase transition state analog, causes non-lethal attenuation of growth in Staphylococcus aureus
    Christopher F Stratton
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461
    Bioinformation 9:9-17. 2013
    ..In addition, the treatment of Staphylococcus aureus cultures with immucillin-H, a powerful inhibitor of PNP, resulted in the non-lethal attenuation of growth, suggesting that PNP activity is not essential for cell viability...
  3. pmc Transition States, analogues, and drug development
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx New York 10461, United States
    ACS Chem Biol 8:71-81. 2013
    ..Analogues of the transition state can bind millions of times more tightly than substrates and show promise for drug development for several targets...
  4. doi request reprint Enzymatic transition states, transition-state analogs, dynamics, thermodynamics, and lifetimes
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Annu Rev Biochem 80:703-32. 2011
    ..Binding isotope effects (BIEs) reveal relative reactant and transition-state analog binding distortion for comparison with actual transition states...
  5. ncbi request reprint Energetic mapping of transition state analogue interactions with human and Plasmodium falciparum purine nucleoside phosphorylases
    Andrzej Lewandowicz
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 280:30320-8. 2005
    ..Specific atomic modifications in the transition state analogues cause disproportionate binding differences between huPNP and PfPNPs and pinpoint energetic binding differences despite similar transition states...
  6. pmc Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases
    Yong Zhang
    From the Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 and
    J Biol Chem 288:34746-54. 2013
    ..These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum...
  7. doi request reprint Tryptophan-free human PNP reveals catalytic site interactions
    Mahmoud Ghanem
    Departments of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 47:3202-15. 2008
    ....
  8. pmc Structure and inhibition of a quorum sensing target from Streptococcus pneumoniae
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 45:12929-41. 2006
    ..coli enzyme. Catalytic site efficiency is primarily responsible for this difference since k(cat)/K(m) for S. pneumoniae MTAN is decreased 845-fold relative to that of E. coli MTAN...
  9. ncbi request reprint Over-the-barrier transition state analogues and crystal structure with Mycobacterium tuberculosis purine nucleoside phosphorylase
    Andrzej Lewandowicz
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 42:6057-66. 2003
    ..This approach has resulted in the highest affinity transition state analogues known for MtPNP...
  10. ncbi request reprint Assignment of downfield proton resonances in purine nucleoside phosphorylase immucillin-H complex by saturation-transferred NOEs
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 43:1980-7. 2004
    ..Since the binding affinity to hPNP for 6-thio-ImmH is decreased 440-fold relative to that for ImmH, the loss in binding energy is primarily due to the hydrogen bond energy loss at the 6-thiol...
  11. ncbi request reprint Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function
    Wuxian Shi
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA
    J Biol Chem 279:18103-6. 2004
    ..The catalytic features of PfPNP indicate a dual cellular function in purine salvage and polyamine metabolism. Combined metabolic functions in a single enzyme strengthen the rationale for targeting PfPNP in anti-malarial action...
  12. ncbi request reprint Atomic dissection of the hydrogen bond network for transition-state analogue binding to purine nucleoside phosphorylase
    Greg A Kicska
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 41:14489-98. 2002
    ..Groups involved in leaving group activation and ribooxacarbenium ion stabilization are central to the H-bond network that provides transition-state stabilization and tight binding of the immucillins...
  13. ncbi request reprint Picomolar inhibitors as transition-state probes of 5'-methylthioadenosine nucleosidases
    Jemy A Gutierrez
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, 10461, USA
    ACS Chem Biol 2:725-34. 2007
    ..Comparing K d ratios for mimics of early and late transition states removes limitations inherent to the enzyme and provides a better predictive tool in discriminating between possible transition-state structures...
  14. ncbi request reprint Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Biochemistry 43:9-18. 2004
    ..These slow-onset, tight-binding transition state analogue inhibitors are the most powerful reported for MTAP and have sufficient affinity to be useful in inhibiting the polyamine pathway...
  15. pmc L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase
    Agnes Rinaldo-Matthis
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Am Chem Soc 130:842-4. 2008
    ....
  16. pmc Four generations of transition-state analogues for human purine nucleoside phosphorylase
    Meng Chiao Ho
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 107:4805-12. 2010
    ..Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP...
  17. ncbi request reprint Enzymatic transition states: thermodynamics, dynamics and analogue design
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Arch Biochem Biophys 433:13-26. 2005
    ..The success of transition state analogue inhibitor design based on kinetic isotope effects validates this approach to understanding enzymatic transition states...
  18. ncbi request reprint Ionic states of substrates and transition state analogues at the catalytic sites of N-ribosyltransferases
    Anthony A Sauve
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 42:5694-705. 2003
    ..Substrate complexes, even in catalytically cycling equilibrium mixtures, do not reveal similar distortions...
  19. pmc Loop-tryptophan human purine nucleoside phosphorylase reveals submillisecond protein dynamics
    Mahmoud Ghanem
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 48:3658-68. 2009
    ..F159W-Leuko-PNP provides a novel protein platform to investigate the protein conformational dynamics occurring prior to transition state formation...
  20. pmc A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT
    Emmanuel S Burgos
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 106:13748-53. 2009
    ....
  21. pmc Transition state analogue discrimination by related purine nucleoside phosphorylases
    Erika A Taylor Ringia
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Am Chem Soc 128:7126-7. 2006
    ..This finding is remarkable since crystallographic analysis indicates complete conservation of active site residues and contacts to ligands in human and bovine PNPs...
  22. doi request reprint Altered thermodynamics from remote mutations altering human toward bovine purine nucleoside phosphorylase
    Mahmoud Ghanem
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 47:2559-64. 2008
    ..Luo, M., Ghanem, M., Taylor, E. A., and Schramm, V. L. (2008) Biochemistry 47, 2577-2583) report changes in transition-state structure as a consequence of mutations remote from the catalytic sites of both HsPNP and BtPNP...
  23. ncbi request reprint Targeting a novel Plasmodium falciparum purine recycling pathway with specific immucillins
    Li Min Ting
    Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 280:9547-54. 2005
    ..falciparum in culture. Immucillins are currently in clinical trials for other indications and may also have application as anti-malarials...
  24. pmc Conformational states of human purine nucleoside phosphorylase at rest, at work, and with transition state analogues
    Achelle A Edwards
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 49:2058-67. 2010
    ..Close mimics of the transition state are hypothesized to retain enzymatic dynamic motions related to transition state formation...
  25. pmc Purine and pyrimidine pathways as targets in Plasmodium falciparum
    María Belén Cassera
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, USA
    Curr Top Med Chem 11:2103-15. 2011
    ..These features reduce two of the major problems with the current antimalarials. Transition state analogue design is being applied to generate new lead compounds to treat malaria by targeting purine and pyrimidine pathways...
  26. ncbi request reprint Anopheles gambiae purine nucleoside phosphorylase: catalysis, structure, and inhibition
    Erika A Taylor
    Department of Biochemistry, Albert Einstein College of Medicine at Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 46:12405-15. 2007
    ..The distance from the N1' cation to the phosphate O4 anion is shorter in the AgPNP.DADMe-ImmH.PO4 complex than in HsPNP.DADMe-ImmH.SO4, offering one explanation for the stronger inhibitory effect of DADMe-ImmH for AgPNP...
  27. ncbi request reprint Inhibition of ricin A-chain with pyrrolidine mimics of the oxacarbenium ion transition state
    Setu Roday
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 43:4923-33. 2004
    ..On the basis of inhibition data and substrate specificity studies, the 2'-hydroxyl group at the depurination site seems to be critical for recruitment as well as catalysis by RTA...
  28. pmc Acyclic immucillin phosphonates: second-generation inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
    Keith Z Hazleton
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA
    Chem Biol 19:721-30. 2012
    ..The AIP prodrugs block proliferation of cultured parasites by inhibiting the incorporation of hypoxanthine into the parasite nucleotide pool and validates HGXPRT as a target in malaria...
  29. pmc Malaria parasite type 4 equilibrative nucleoside transporters (ENT4) are purine transporters with distinct substrate specificity
    I J Frame
    Department of Physiology and Biophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA
    Biochem J 446:179-90. 2012
    ..Its role in parasite physiology remains uncertain, but is likely to be significant because of the strong conservation of ENT4 homologues in Plasmodia genomes...
  30. pmc Entropy-driven binding of picomolar transition state analogue inhibitors to human 5'-methylthioadenosine phosphorylase
    Rong Guan
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, United States
    Biochemistry 50:10408-17. 2011
    ....
  31. ncbi request reprint Structural and kinetic characterization of Escherichia coli TadA, the wobble-specific tRNA deaminase
    Jungwook Kim
    Department of Biochemistry, Center for Synchrotron Biosciences, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 45:6407-16. 2006
    ..This work begins to define the chemical and structural determinants responsible for catalysis and substrate recognition and lays the foundation for detailed mechanistic analysis of this essential enzyme...
  32. ncbi request reprint SIR2: the biochemical mechanism of NAD(+)-dependent protein deacetylation and ADP-ribosyl enzyme intermediates
    Anthony A Sauve
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Ave F304, Bronx, NY 10461, USA
    Curr Med Chem 11:807-26. 2004
    ..The present review describes the current knowledge of the Sir2 reaction, the reaction mechanism and the regulation of Sir2...
  33. pmc Structural and metabolic specificity of methylthiocoformycin for malarial adenosine deaminases
    Meng Chiao Ho
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, USA
    Biochemistry 48:9618-26. 2009
    ..Treatment of P. falciparum cultures with coformycin or MT-coformycin in the presence of MTA is effective in inhibiting parasite growth...
  34. pmc Methylthioadenosine deaminase in an alternative quorum sensing pathway in Pseudomonas aeruginosa
    Rong Guan
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461, United States
    Biochemistry 51:9094-103. 2012
    ....
  35. pmc Immucillins in custom catalytic-site cavities
    Andrew S Murkin
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Bioorg Med Chem Lett 18:5900-3. 2008
    ..Hydrophobic 5'-substituted Immucillins are transition-state analogue inhibitors of this mutant enzyme. Dissociation constants as low as 2pM are achieved, with K(m)/K(d) as high as 400,000,000...
  36. ncbi request reprint Active site contacts in the purine nucleoside phosphorylase--hypoxanthine complex by NMR and ab initio calculations
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 43:15966-74. 2004
    ..This approach has the potential to become a high-resolution tool for structural determination...
  37. pmc Altered enthalpy-entropy compensation in picomolar transition state analogues of human purine nucleoside phosphorylase
    Achelle A Edwards
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 48:5226-38. 2009
    ..Via introduction of flexibility into the inhibitor structure, the enthalpy-entropy compensation pattern is altered to permit tighter binding...
  38. doi request reprint Second-sphere amino acids contribute to transition-state structure in bovine purine nucleoside phosphorylase
    Lei Li
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 47:2577-83. 2008
    ..These residues are implicated in linking the dynamic motion of the protein to formation of the transition state...
  39. pmc Transport of purines and purine salvage pathway inhibitors by the Plasmodium falciparum equilibrative nucleoside transporter PfENT1
    Paul M Riegelhaupt
    Department of Physiology and Biophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA
    Mol Biochem Parasitol 169:40-9. 2010
    ..These results provide new insights into PfENT1 and the mechanism by which purine salvage pathway inhibitors are transported into the parasite cytoplasm...
  40. ncbi request reprint Phosphate activation in the ground state of purine nucleoside phosphorylase
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 128:7765-71. 2006
    ..The electronic structure of phosphate bound with a transition state analogue differs substantially from that in the Michaelis complexes...
  41. pmc Erythrocytic adenosine monophosphate as an alternative purine source in Plasmodium falciparum
    Maria B Cassera
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, USA
    J Biol Chem 283:32889-99. 2008
    ..falciparum nucleoside transporter PfNT1 established that this transporter does not transport AMP. These metabolic patterns establish the existence of a novel nucleoside monophosphate transport pathway in P. falciparum...
  42. doi request reprint Femtomolar inhibitors bind to 5'-methylthioadenosine nucleosidases with favorable enthalpy and entropy
    Keisha Thomas
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Biochemistry 51:7541-50. 2012
    ..We conclude that factors other than first-sphere catalytic residue contacts contribute to binding of inhibitors because the thermodynamic signature differs between bacterial species of the same enzyme...
  43. ncbi request reprint Transition state structure of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Escherichia coli and its similarity to transition state analogues
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 44:11647-59. 2005
    ..Transition state analogues that resemble this transition state structure are powerful inhibitors, and their molecular electrostatic potential maps closely resemble that of the transition state...
  44. doi request reprint Transition state structure of E. coli tRNA-specific adenosine deaminase
    Minkui Luo
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Am Chem Soc 130:2649-55. 2008
    ..The ecTadA transition state structure reveals the detailed architecture for enzymatic catalysis. This approach should be readily transferable for transition state characterization of other RNA editing enzymes...
  45. ncbi request reprint Activating the phosphate nucleophile at the catalytic site of purine nucleoside phosphorylase: a vibrational spectroscopic study
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 126:9516-7. 2004
    ....
  46. pmc Growth and metastases of human lung cancer are inhibited in mouse xenografts by a transition state analogue of 5'-methylthioadenosine phosphorylase
    Indranil Basu
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA
    J Biol Chem 286:4902-11. 2011
    ..MTDIA antitumor activity in xenografts supports MTAP as a target for lung cancer therapy...
  47. pmc A high-affinity adenosine kinase from Anopheles gambiae
    Maria B Cassera
    Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, United States
    Biochemistry 50:1885-93. 2011
    ..mRNA analysis verifies that AgAK transcripts are produced in the adult insects...
  48. ncbi request reprint Immucillins as antibiotics for T-cell proliferation and malaria
    Vern L Schramm
    Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, USA
    Nucleosides Nucleotides Nucleic Acids 23:1305-11. 2004
    ..Immucillins also inhibit PNP from Plasmodium falciparum. Parasites cultured in human erythrocytes are killed by purine starvation in the presence of Immucillins and can be rescued by hypoxanthine...
  49. pmc Femtosecond dynamics coupled to chemical barrier crossing in a Born-Oppenheimer enzyme
    Rafael G Silva
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 108:18661-5. 2011
    ..This study demonstrates coupling of enzymatic bond vibrations on the femtosecond time scale to barrier crossing...
  50. pmc Atomic detail of chemical transformation at the transition state of an enzymatic reaction
    Suwipa Saen-oon
    Departments of Biophysics and Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 105:16543-8. 2008
    ..Dynamic motions on the femtosecond timescale provide the simultaneous optimization of these effects and coincide with transition state formation...
  51. pmc Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing
    Jemy A Gutierrez
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Chem Biol 5:251-7. 2009
    ..These results support MTAN's role in quorum sensing and its potential as a target for bacterial anti-infective drug design...
  52. pmc Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues
    Agnes Rinaldo-Matthis
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 46:659-68. 2007
    ..And this difference is explained by isotope-edited difference infrared spectroscopy with [6-18O]ImmH to establish that O6 is the keto tautomer in TvPNP x ImmH x PO4, causing an unfavorable leaving-group interaction...
  53. ncbi request reprint Inhibitors of ADP-ribosylating bacterial toxins based on oxacarbenium ion character at their transition states
    Guo Chun Zhou
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Am Chem Soc 126:5690-8. 2004
    ..The origin of this similarity is proposed to reside in the cationic nature of NAD(+) both as substrate and at the transition state...
  54. pmc Pyrophosphate activation in hypoxanthine--guanine phosphoribosyltransferase with transition state analogue
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 49:2705-14. 2010
    ....
  55. ncbi request reprint Ricin A-chain activity on stem-loop and unstructured DNA substrates
    Tim K Amukele
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 44:4416-25. 2005
    ..1 A, and the former is proposed to place them in a catalytically favorable configuration. The ability to use short RNA-DNA hybrids as substrates for RTA permits exploration of related structures to function as substrates and inhibitors...
  56. pmc Neighboring group participation in the transition state of human purine nucleoside phosphorylase
    Andrew S Murkin
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 46:5038-49. 2007
    ..These surprising results establish that forces in the Michaelis complex, reported by the BIEs, can be reversed or enhanced at the transition state...
  57. pmc Remote mutations and active site dynamics correlate with catalytic properties of purine nucleoside phosphorylase
    Suwipa Saen-oon
    Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biophys J 94:4078-88. 2008
    ..That motion and catalysis are enhanced by mutations remote from the catalytic site implicates dynamic coupling through the protein architecture as a component of catalysis in hPNP...
  58. ncbi request reprint Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition
    Anthony A Sauve
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Mol Cell 17:595-601. 2005
    ..Thus, a nicotinamide antagonist is a Sir2 agonist in vitro and in vivo...
  59. pmc Thermodynamic analysis of transition-state features in picomolar inhibitors of human 5'-methylthioadenosine phosphorylase
    Rong Guan
    From the Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461, United States
    Biochemistry 52:8313-22. 2013
    ..The enthalpic, entropic, and protein-stability features of TS analogue binding to human MTAP are resolved in these studies. ..
  60. pmc Catalytic site conformations in human PNP by 19F-NMR and crystallography
    Javier Suarez
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Chem Biol 20:212-22. 2013
    ..Specific (19)F-Trp labels and X-ray crystallography provide multidimensional characterization of conformational states for free, catalytic, and inhibited complexes of human PNP...
  61. ncbi request reprint Insight into catalytically relevant correlated motions in human purine nucleoside phosphorylase
    Sara Nunez
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Phys Chem A 110:463-72. 2006
    ..However, further structural data for the hPNP mutants are needed to confirm our hypothesis...
  62. pmc Constrained bonding environment in the Michaelis complex of Trypanosoma cruzi uridine phosphorylase
    Rafael G Silva
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Biochemistry 51:6715-7. 2012
    ..This conformer differs in sugar pucker and uracil orientation from the unbound conformer and the transition-state structure. These results support ground-state stabilization in the Michaelis complex...
  63. pmc Pyrophosphate interactions at the transition states of Plasmodium falciparum and human orotate phosphoribosyltransferases
    Yong Zhang
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Am Chem Soc 132:8787-94. 2010
    ..We propose that the transition state similarity with different nucleophiles is determined, in part, by the geometric constraints imposed by the catalytic sites...
  64. doi request reprint Remote mutations alter transition-state structure of human purine nucleoside phosphorylase
    Minkui Luo
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 47:2565-76. 2008
    ..Dynamic coupling motions from the remote mutations to the catalytic sites are proposed...
  65. ncbi request reprint Transition state analysis for human and Plasmodium falciparum purine nucleoside phosphorylases
    Andrzej Lewandowicz
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 43:1458-68. 2004
    ..The large 5'-(3)H KIE reveals substantial distortion at the 5'-hydroxymethyl group which causes loosening of the C5'-H5' bonds during the reaction coordinate...
  66. ncbi request reprint Enzymatic transition states and transition state analogues
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Curr Opin Struct Biol 15:604-13. 2005
    ..Stable analogues similar to the transition state capture dynamic excursions that generate the transition state and convert them into thermodynamic binding energy. These analogues bind with extraordinary affinity relative to reactants...
  67. ncbi request reprint Transition state analogue inhibitors of purine nucleoside phosphorylase from Plasmodium falciparum
    Gregory A Kicska
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 277:3219-25. 2002
    ..These properties of P. falciparum PNP are consistent with a metabolic role in purine salvage and provide an explanation for the antibiotic effect of the immucillins on P. falciparum cultured in human erythrocytes...
  68. ncbi request reprint Acyclic ribooxacarbenium ion mimics as transition state analogues of human and malarial purine nucleoside phosphorylases
    Erika A Taylor
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Am Chem Soc 129:6984-5. 2007
    ..The best third generation inhibitor is equivalent to the best inhibitors found in the previous transition state analogues...
  69. ncbi request reprint Binding causes the remote [5'-3H]thymidine kinetic isotope effect in human thymidine phosphorylase
    Matthew R Birck
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 126:6882-3. 2004
    ..Here we report equilibrium binding isotope effects sufficiently large to explain the presence of this substantial KIE in thymidine phosphorylase...
  70. doi request reprint Transition-state interactions revealed in purine nucleoside phosphorylase by binding isotope effects
    Andrew S Murkin
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA
    J Am Chem Soc 130:2166-7. 2008
  71. pmc Ribocation transition state capture and rebound in human purine nucleoside phosphorylase
    Mahmoud Ghanem
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Chem Biol 16:971-9. 2009
    ..These results establish a ribocation lifetime too short to permit capture by water. An enlarged catalytic site permits ribocation formation with relaxed geometric constraints, permitting nucleophilic rebound and N3-inosine isomerization...
  72. pmc Enzymatic transition states and dynamic motion in barrier crossing
    Steven D Schwartz
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Chem Biol 5:551-8. 2009
    ....
  73. pmc Plasmodium falciparum purine nucleoside phosphorylase is critical for viability of malaria parasites
    Dennis C Madrid
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 283:35899-907. 2008
    ..The results demonstrate the importance of purine salvage in P. falciparum and validate PfPNP as the target of immucillins...
  74. ncbi request reprint Transition states and inhibitors of the purine nucleoside phosphorylase family
    Erika A Taylor Ringia
    Department of Biochemistry, Albert Einstein College of Medicine of the Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Curr Top Med Chem 5:1237-58. 2005
    ..Comparison of the transition states and substrate specificity of various PNPs permits the design of species-specific inhibitors for use as therapeutic agents...
  75. pmc Leaving group activation and pyrophosphate ionic state at the catalytic site of Plasmodium falciparum orotate phosphoribosyltransferase
    Yong Zhang
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, United States
    J Am Chem Soc 132:17023-31. 2010
    ..These results along with previous PfOPRT transition-state analyses provide reaction coordinate information for the PfOPRT-catalyzed OMP pyrophosphorolysis reaction...
  76. pmc Transition states of Plasmodium falciparum and human orotate phosphoribosyltransferases
    Yong Zhang
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Am Chem Soc 131:4685-94. 2009
    ..p-Nitrophenyl beta-D-ribose 5'-phosphate is a poor substrate of PfOPRT and HsOPRT but is a nanomolar inhibitor, supporting a reaction coordinate with strong leaving group activation...
  77. ncbi request reprint Closed site complexes of adenine phosphoribosyltransferase from Giardia lamblia reveal a mechanism of ribosyl migration
    Wuxian Shi
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 277:39981-8. 2002
    ..1-A excursion of the ribosyl anomeric carbon, whereas the adenine ring and the 5-phosphoryl group remained fixed. G. lamblia APRTase therefore provides another example of nucleophilic displacement by electrophile migration...
  78. ncbi request reprint Promoting vibrations in human purine nucleoside phosphorylase. A molecular dynamics and hybrid quantum mechanical/molecular mechanical study
    Sara Nunez
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 126:15720-9. 2004
    ....
  79. ncbi request reprint Purine-less death in Plasmodium falciparum induced by immucillin-H, a transition state analogue of purine nucleoside phosphorylase
    Gregory A Kicska
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 277:3226-31. 2002
    ..The IC(50) values for immucillin analogue toxicity to P. falciparum cultures indicate that inhibition of PNP in both the erythrocytes and the parasite is necessary to induce a purine-less death...
  80. ncbi request reprint Transition state structure for ADP-ribosylation of eukaryotic elongation factor 2 catalyzed by diphtheria toxin
    Sapan L Parikh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 43:1204-12. 2004
    ..The transition state model presented here is asymmetric and consistent with a dissociative S(N)1 type mechanism in which attack of the diphthamide nucleophile lags behind departure of the nicotinamide...
  81. ncbi request reprint Femtomolar transition state analogue inhibitors of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Escherichia coli
    Vipender Singh
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 280:18265-73. 2005
    ..The accompanying article reports crystal structures of MTAN with these analogues...
  82. ncbi request reprint Enzymatic transition state poise and transition state analogues
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Acc Chem Res 36:588-96. 2003
    ..Binding strengths of transition state analogues are readily correlated with transition state poise...
  83. pmc Weak coupling of ATP hydrolysis to the chemical equilibrium of human nicotinamide phosphoribosyltransferase
    Emmanuel S Burgos
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 47:11086-96. 2008
    ..NMN synthesis by NAMPT is powerfully inhibited by both NAD (+) ( K i = 0.14 muM) and NADH ( K i = 0.22 muM), an apparent regulatory feedback mechanism...
  84. pmc Binding isotope effects: boon and bane
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, United States
    Curr Opin Chem Biol 11:529-36. 2007
    ..Although binding isotope effects complicate kinetic isotope effect analysis, they also provide a powerful tool for finding atomic distortion in molecular interactions...
  85. ncbi request reprint Development of transition state analogues of purine nucleoside phosphorylase as anti-T-cell agents
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forch 308, Bronx, NY 10461, USA
    Biochim Biophys Acta 1587:107-17. 2002
    ..Immucillins are capable of providing complete control of in vivo PNP levels and hold promise for treatment of proliferative T-cell disorders...
  86. pmc Vinyldeoxyadenosine in a sarcin-ricin RNA loop and its binding to ricin toxin a-chain
    Setu Roday
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 46:6169-82. 2007
    ..Unlike RTA, PAP catalyzes the slow release of 8-vinyladenine from 8vdA-10. The isolation of 8-vA and its physicochemical characterization is described...
  87. ncbi request reprint Nucleophilic participation in the transition state for human thymidine phosphorylase
    Matthew R Birck
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue Bronx, New York 10461, USA
    J Am Chem Soc 126:2447-53. 2004
    ....
  88. ncbi request reprint Enzymatic transition state theory and transition state analogue design
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 282:28297-300. 2007
  89. pmc Transition states for glucopyranose interconversion
    Brett E Lewis
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 128:5049-58. 2006
    ..We have found the transition states for anomerization, and we have also concluded that it is forbidden for the water molecule to form a hydrogen bond bridge to both OH1 and O5 of glucose simultaneously in either transition state...
  90. ncbi request reprint Phosphoribosyltransferase mechanisms and roles in nucleic acid metabolism
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA
    Prog Nucleic Acid Res Mol Biol 78:261-304. 2004