apoenzymes

Summary

Summary: The protein components of enzyme complexes (HOLOENZYMES). An apoenzyme is the holoenzyme minus any cofactors (ENZYME COFACTORS) or prosthetic groups required for the enzymatic function.

Top Publications

  1. Sanli G, Blaber M. Structural assembly of the active site in an aldo-keto reductase by NADPH cofactor. J Mol Biol. 2001;309:1209-18 pubmed
    ..Thus, NADPH functions not only to provide a hydride ion for catalytic reduction, but is also a critical structural component for formation of a catalytically competent form of DKGR A. ..
  2. Stathopulos P, Rumfeldt J, Karbassi F, Siddall C, Lepock J, Meiering E. Calorimetric analysis of thermodynamic stability and aggregation for apo and holo amyotrophic lateral sclerosis-associated Gly-93 mutants of superoxide dismutase. J Biol Chem. 2006;281:6184-93 pubmed
    ..This suggests that the mutations cause apo-SOD to have an increased propensity to misfold or aggregate, which may be linked to increased toxic mutant SOD aggregation in fALS. ..
  3. Kavanagh K, Klimacek M, Nidetzky B, Wilson D. The structure of apo and holo forms of xylose reductase, a dimeric aldo-keto reductase from Candida tenuis. Biochemistry. 2002;41:8785-95 pubmed
    ..Modeling of xylose into the active site of the holoenzyme using ordered waters as a guide for sugar hydroxyls suggests a convincing mode of substrate binding. ..
  4. Lindberg M, Normark J, Holmgren A, Oliveberg M. Folding of human superoxide dismutase: disulfide reduction prevents dimerization and produces marginally stable monomers. Proc Natl Acad Sci U S A. 2004;101:15893-8 pubmed
    ..Thus, impaired ability to form, or retain, the C57-C146 bond in vivo is predicted to increase the cellular load of marginally stable apoSOD monomers, which may have implications for the amytrophic lateral sclerosis neuropathology. ..
  5. Yang C, Jas G, Kuczera K. Structure, dynamics and interaction with kinase targets: computer simulations of calmodulin. Biochim Biophys Acta. 2004;1697:289-300 pubmed
    ..This explains why the observed entropic contribution to the binding free energy is small and positive, and not large and negative as expected for a complex with such extensive hydrophobic contacts. ..
  6. Yun M, Park C, Kim J, Park H. Structural analysis of glyceraldehyde 3-phosphate dehydrogenase from Escherichia coli: direct evidence of substrate binding and cofactor-induced conformational changes. Biochemistry. 2000;39:10702-10 pubmed
    ..This finding suggests that the cofactor NAD(+) may stabilize the transition state oxyanion of the hemiacetal intermediate in support of the flip-flop model for GAP binding...
  7. Han M, Zhang J. Class I phospho-inositide-3-kinases (PI3Ks) isoform-specific inhibition study by the combination of docking and molecular dynamics simulation. J Chem Inf Model. 2010;50:136-45 pubmed publisher
    ..The work provides a possible effective pharmacophore model for PI3Kalpha inhibitor. The dynamic behaviors of the LY294002-bound PI3Ks are studied too. ..
  8. Tokuoka K, Kusakari Y, Krungkrai S, Matsumura H, Kai Y, Krungkrai J, et al. Structural basis for the decarboxylation of orotidine 5'-monophosphate (OMP) by Plasmodium falciparum OMP decarboxylase. J Biochem. 2008;143:69-78 pubmed
    ..The structural basis of substrate or product binding to PfOMPDC will help to uncover the decarboxylation mechanism and facilitate structure-based optimization of antimalarial drugs. ..
  9. Malerba F, Bellelli A, Giorgi A, Bossa F, Contestabile R. The mechanism of addition of pyridoxal 5'-phosphate to Escherichia coli apo-serine hydroxymethyltransferase. Biochem J. 2007;404:477-85 pubmed

More Information

Publications62

  1. Dassama L, Krebs C, Bollinger J, Rosenzweig A, Boal A. Structural basis for assembly of the Mn(IV)/Fe(III) cofactor in the class Ic ribonucleotide reductase from Chlamydia trachomatis. Biochemistry. 2013;52:6424-36 pubmed publisher
    ..2 Å) Mn(II)-Fe(II) interionic distance, promoting formation of the Mn(IV)/Fe(IV) activation intermediate. ..
  2. Li D, Zhang J, Hou Y, Liu L, Liu S, Liu W. Crystallization and preliminary crystallographic analysis of 2-aminophenol 1,6-dioxygenase complexed with substrate and with an inhibitor. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68:1337-40 pubmed publisher
    ..24, b=48.39, c=108.55?Å, ?=109.57°. All X-ray data sets collected from diffraction-quality crystals were suitable for structure determination...
  3. Shirran S, Barran P. The use of ESI-MS to probe the binding of divalent cations to calmodulin. J Am Soc Mass Spectrom. 2009;20:1159-71 pubmed publisher
    ..This work demonstrates the affinity for calcium above all other metals, but also warns about the ability of lead to replace calcium with apparent ease...
  4. Williams N, Lucet I, Klinken S, Ingley E, Rossjohn J. Crystal structures of the Lyn protein tyrosine kinase domain in its Apo- and inhibitor-bound state. J Biol Chem. 2009;284:284-91 pubmed publisher
    ..Accordingly, our data provide valuable information for the further development of therapeutics targeting Lyn and the important Src-family of kinases. ..
  5. Banci L, Bertini I, D Amelio N, Libralesso E, Turano P, Valentine J. Metalation of the amyotrophic lateral sclerosis mutant glycine 37 to arginine superoxide dismutase (SOD1) apoprotein restores its structural and dynamical properties in solution to those of metalated wild-type SOD1. Biochemistry. 2007;46:9953-62 pubmed
    ..These results suggest further that it is the metal-free apo forms of the mutant SOD1 protein that are the agents of its toxicity. ..
  6. Benoit S, Mehta N, Weinberg M, Maier C, Maier R. Interaction between the Helicobacter pylori accessory proteins HypA and UreE is needed for urease maturation. Microbiology. 2007;153:1474-82 pubmed
    ..pylori. ..
  7. Sakai H, Tsukamoto T, Yamamoto M, Shirai N, Iidaka T, Yanai T, et al. Differential effects of partial hepatectomy and carbon tetrachloride administration on induction of liver cell foci in a model for detection of initiation activity. Jpn J Cancer Res. 2001;92:1018-25 pubmed
    ..In conclusion, PH was able to induce cell proliferation with maintenance of CYP 2E1, therefore being advantageous for induction of liver cell foci in models to detect initiation activity. ..
  8. Kottom T, Thomas C, Limper A. Characterization of Pneumocystis carinii PHR1, a pH-regulated gene important for cell wall Integrity. J Bacteriol. 2001;183:6740-5 pubmed
    ..cerevisiae gas1 mutants under lethal conditions of cell wall stress. These results indicate that P. carinii PHR1 encodes a protein responsive to environmental pH and capable of mediating fungal cell wall integrity. ..
  9. Lin Y, St Maurice M. The structure of allophanate hydrolase from Granulibacter bethesdensis provides insights into substrate specificity in the amidase signature family. Biochemistry. 2013;52:690-700 pubmed publisher
    ..Analysis of the AH active site architecture offers new insights into common determinants of catalysis and specificity among divergent members of the amidase signature family...
  10. Shi R, Munger C, Asinas A, Benoit S, Miller E, Matte A, et al. Crystal structures of apo and metal-bound forms of the UreE protein from Helicobacter pylori: role of multiple metal binding sites. Biochemistry. 2010;49:7080-8 pubmed publisher
    ..Therefore, the ability of the improved Ni(2+)-binding versions to deliver more nickel is likely an effect of an increased local concentration of metal ions that can rapidly replenish transferred ions bound to His102. ..
  11. Shimon L, Rabinkov A, Shin I, Miron T, Mirelman D, Wilchek M, et al. Two structures of alliinase from Alliium sativum L.: apo form and ternary complex with aminoacrylate reaction intermediate covalently bound to the PLP cofactor. J Mol Biol. 2007;366:611-25 pubmed
  12. Tang C, Jeffers C, Nichols J, Tu S. Flavin specificity and subunit interaction of Vibrio fischeri general NAD(P)H-flavin oxidoreductase FRG/FRase I. Arch Biochem Biophys. 2001;392:110-6 pubmed
    ..Many aspects of these properties are compared with a structurally and functionally related Vibrio harveyi NADPH-specific flavin reductase FRP. ..
  13. HOM K, Heinzl G, Eakanunkul S, Lopes P, Xue F, MacKerell A, et al. Small molecule antivirulents targeting the iron-regulated heme oxygenase (HemO) of P. aeruginosa. J Med Chem. 2013;56:2097-109 pubmed publisher
    ..Furthermore, 5 showed antimicrobial activity in the in vivo C. elegans curing assay. Thus, targeting virulence mechanisms required within the host is a viable antimicrobial strategy for the development of novel antivirulants. ..
  14. Fruk L, Kuo C, Torres E, Niemeyer C. Apoenzyme reconstitution as a chemical tool for structural enzymology and biotechnology. Angew Chem Int Ed Engl. 2009;48:1550-74 pubmed publisher
    ..Nowadays a large variety of synthetic cofactors can be used for the reconstitution of apoenzymes and, thus, generate novel semisynthetic enzymes...
  15. Lee J, Na Y, Song H, Kim D, Park B, Rho S, et al. Crystal structure of the apo form of D-alanine: D-alanine ligase (Ddl) from Thermus caldophilus: a basis for the substrate-induced conformational changes. Proteins. 2006;64:1078-82 pubmed publisher
  16. Tsuji E, Okazaki K, Isaji M, Takeda K. Crystal structures of the apo and holo form of rat catechol-O-methyltransferase. J Struct Biol. 2009;165:133-9 pubmed publisher
    ..These conformational changes provide a deeper insight into the structural events occurring in reactions catalyzed by AdoMet. ..
  17. Bist P, Sistla S, Krishnamurthy V, Acharya A, Chandrakala B, Rao D. S-adenosyl-L-methionine is required for DNA cleavage by type III restriction enzymes. J Mol Biol. 2001;310:93-109 pubmed
    ..Taken together, these results suggest that AdoMet binding causes conformational changes in the restriction enzyme and is necessary to bring about DNA cleavage. ..
  18. Sheu Y, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24:101-13 pubmed
    ..We suggest that DDK docks on and phosphorylates MCM proteins at licensed origins to promote proper assembly of pre-IC. ..
  19. Arutiunova E, Pleten A, Nagradova N, Muronetz V. Antibodies to inactive conformations of glyceraldehyde-3-phosphate dehydrogenase inactivate the apo- and holoforms of the enzyme. Biochemistry (Mosc). 2006;71:685-91 pubmed
  20. Tu J, Chin K, Wang A, Chou S. Unique GTP-binding pocket and allostery of uridylate kinase from a gram-negative phytopathogenic bacterium. J Mol Biol. 2009;385:1113-26 pubmed publisher
    ..campestris UMPK, similar to that suggested for the effect of ATP effector on B. anthracis UMPK. ..
  21. Smeller L, Meersman F, Fidy J, Heremans K. High-pressure FTIR study of the stability of horseradish peroxidase. Effect of heme substitution, ligand binding, Ca++ removal, and reduction of the disulfide bonds. Biochemistry. 2003;42:553-61 pubmed
  22. Tran L, Broadhurst R, Tosin M, Cavalli A, Weissman K. Insights into protein-protein and enzyme-substrate interactions in modular polyketide synthases. Chem Biol. 2010;17:705-16 pubmed publisher
  23. Sim L, Quezada Calvillo R, Sterchi E, Nichols B, Rose D. Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol. 2008;375:782-92 pubmed
    ..The results provide a structural basis for the complementary roles of these glycosyl hydrolase family 31 subunits in the bioprocessing of complex starch structures into glucose. ..
  24. Spolaore B, Bermejo R, Zambonin M, Fontana A. Protein interactions leading to conformational changes monitored by limited proteolysis: apo form and fragments of horse cytochrome c. Biochemistry. 2001;40:9460-8 pubmed
    ..Finally, a specific interest of the cyt c fragment system herewith investigated resides in the fact that the fragments are exactly the exon products of the cyt c gene. ..
  25. Alicea Velázquez N, Boggon T. SHP family protein tyrosine phosphatases adopt canonical active-site conformations in the apo and phosphate-bound states. Protein Pept Lett. 2013;20:1039-48 pubmed
    ..8 Å crystal structure of the SHP-1 catalytic domain in complex with a phosphate ion. We provide structural analysis for the WPD loop closed state of SHP phosphatases and the conformational changes that occur upon WPD loop closure. ..
  26. Burk D, Hon W, Leung A, Berghuis A. Structural analyses of nucleotide binding to an aminoglycoside phosphotransferase. Biochemistry. 2001;40:8756-64 pubmed
    ..This alternate binding mode is likely a conserved feature among aminoglycoside kinases and could be exploited for the structure-based drug design of compounds to combat antibiotic resistance...
  27. Danielsson J, Kurnik M, Lang L, Oliveberg M. Cutting off functional loops from homodimeric enzyme superoxide dismutase 1 (SOD1) leaves monomeric ?-barrels. J Biol Chem. 2011;286:33070-83 pubmed publisher
    ..Taken together, these data suggest that the cytotoxic function of apoSOD1 does not emerge from its folded ground state but from a high energy intermediate or even from the denatured ensemble. ..
  28. Müller I, Lamers M, Ritchie A, Park H, Dominguez C, Munoz Sanjuan I, et al. A new apo-caspase-6 crystal form reveals the active conformation of the apoenzyme. J Mol Biol. 2011;410:307-15 pubmed publisher
    ..The structural comparison allows us to visualize the organization of loops L2, L3, and L4 upon ligand binding and how the catalytic groove forms to accommodate the inhibitor. ..
  29. Senapati S, Bui J, McCammon J. Induced fit in mouse acetylcholinesterase upon binding a femtomolar inhibitor: a molecular dynamics study. J Med Chem. 2005;48:8155-62 pubmed
    ..These residues in the complex deviate from their positions in unliganded mAChE to better accommodate the inhibitor in the active site gorge. ..
  30. Safo M, Musayev F, Schirch V. Structure of Escherichia coli pyridoxine 5'-phosphate oxidase in a tetragonal crystal form: insights into the mechanistic pathway of the enzyme. Acta Crystallogr D Biol Crystallogr. 2005;61:599-604 pubmed
  31. Fetherolf M, Boyd S, Taylor A, Kim H, Wohlschlegel J, Blackburn N, et al. Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. J Biol Chem. 2017;292:12025-12040 pubmed publisher
    ..Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment. ..
  32. Nauton L, Kahn R, Garau G, Hernandez J, Dideberg O. Structural insights into the design of inhibitors for the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia. J Mol Biol. 2008;375:257-69 pubmed
    ..This structural information could prove essential in the process of elucidation of the mode of interaction between a putative lead compound and metallo-beta-lactamases, one of the main steps in structure-based drug design. ..
  33. Li L, Gao F, Ye J, Chen Z, Li Q, Gao W, et al. FRET-based biofriendly apo-GO(x)-modified gold nanoprobe for specific and sensitive glucose sensing and cellular imaging. Anal Chem. 2013;85:9721-7 pubmed publisher
    ..Due to the low toxicity of this detection system and reliable cellular uptake ability of AuNPs, imaging of intracellular glucose consumption was successfully realized in cancer cells. ..
  34. Yao L, Yan H, Cukier R. Mechanism of dihydroneopterin aldolase: a molecular dynamics study of the apo enzyme and its product complex. J Phys Chem B. 2006;110:1443-56 pubmed
    ..An analysis of the various components that contribute to the exit path energy and entropy provides insight into the energy-entropy compensation for product release. ..
  35. Blanco J, Moore R, Kabaleeswaran V, Viola R. A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae. Protein Sci. 2003;12:27-33 pubmed
    ..The conformational changes that do occur result primarily from NADP binding, and are localized to the repositioning of two surface loops located on the rim at opposite sides of the NADP cleft...
  36. Wu J, Yang J, Kannan N, Madhusudan -, Xuong N, Ten Eyck L, et al. Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helix. Protein Sci. 2005;14:2871-9 pubmed
    ..Finally, based on temperature factors, this mutant structure is more stable than the wild-type C-subunit in the apo state. ..
  37. Stehle T, Sreeramulu S, Lohr F, Richter C, Saxena K, Jonker H, et al. The apo-structure of the low molecular weight protein-tyrosine phosphatase A (MptpA) from Mycobacterium tuberculosis allows for better target-specific drug development. J Biol Chem. 2012;287:34569-82 pubmed publisher
    ..PtkA, the kinase complementary to MptpA, phosphorylates these two tyrosine residues in MptpA. We characterized the MptpA-PtkA interaction by NMR spectroscopy to show that both the P- and D-loop form part of the binding interface. ..
  38. Taylor J, Fawaz R, Ababou A, Williams M, Ladbury J. NMR assignment of the apo and peptide-bound SH2 domain from the Rous sarcoma viral protein Src. J Biomol NMR. 2005;32:339 pubmed
  39. Pathak C, Im H, Yang Y, Yoon H, Kim H, Kwon A, et al. Crystal structure of apo and copper bound HP0894 toxin from Helicobacter pylori 26695 and insight into mRNase activity. Biochim Biophys Acta. 2013;1834:2579-90 pubmed publisher
    ..Glu58 also acts as a general base, and substrate reorientation is caused by Phe88. Based on experimental findings, a model for antitoxin binding could be suggested. ..
  40. Yamada T, Komoto J, Takata Y, Ogawa H, Pitot H, Takusagawa F. Crystal structure of serine dehydratase from rat liver. Biochemistry. 2003;42:12854-65 pubmed
    ..A possible catalytic mechanism involves the phosphate group, surrounded by the characteristic sequence, acting as a general acid to donate a proton to the leaving hydroxyl group of serine. ..
  41. Yeh J, Charrier V, Paulo J, Hou L, Darbon E, Claiborne A, et al. Structures of enterococcal glycerol kinase in the absence and presence of glycerol: correlation of conformation to substrate binding and a mechanism of activation by phosphorylation. Biochemistry. 2004;43:362-73 pubmed
    ..On the basis of our structural results, we propose a mechanism by which the phosphorylation of a histidyl residue located 25 A from the active site results in a 10-15-fold increase in the activity of the enterococcal glycerol kinase. ..
  42. Saha B, Mukherjee S, Das A. Molecular characterization of Mycobacterium tuberculosis cystathionine gamma synthase--apo- and holoforms. Int J Biol Macromol. 2009;44:385-92 pubmed publisher
    ..But it induces tertiary structure stability of the protein thereby counteracting the deleterious effect of denaturant. In silico modelling and cofactor docking provide insights into molecular structure of the enzyme. ..
  43. Liu S, Laliberte F, Bobechko B, Bartlett A, Lario P, Gorseth E, et al. Dissecting the cofactor-dependent and independent bindings of PDE4 inhibitors. Biochemistry. 2001;40:10179-86 pubmed
  44. Petersen J, Small G. A gene required for the novel activation of a class II DNA photolyase in Chlamydomonas. Nucleic Acids Res. 2001;29:4472-81 pubmed
    ..To our knowledge, the requirement for a second gene for full activity of a DNA photolyase is novel. ..
  45. Beermann B, Guddorf J, Boehm K, Albers A, Kolkenbrock S, Fetzner S, et al. Stability, unfolding, and structural changes of cofactor-free 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase. Biochemistry. 2007;46:4241-9 pubmed
  46. Gay L, NG H, Alber T. A conserved dimer and global conformational changes in the structure of apo-PknE Ser/Thr protein kinase from Mycobacterium tuberculosis. J Mol Biol. 2006;360:409-20 pubmed
    ..This structure may represent an inactive conformation stabilized by dimerization or, alternatively, an active conformation that reveals shifts that mediate nucleotide exchange and order substrate binding. ..
  47. Stathopulos P, Rumfeldt J, Scholz G, Irani R, Frey H, Hallewell R, et al. Cu/Zn superoxide dismutase mutants associated with amyotrophic lateral sclerosis show enhanced formation of aggregates in vitro. Proc Natl Acad Sci U S A. 2003;100:7021-6 pubmed
  48. Müller I, Kahnert A, Pape T, Sheldrick G, Meyer Klaucke W, Dierks T, et al. Crystal structure of the alkylsulfatase AtsK: insights into the catalytic mechanism of the Fe(II) alpha-ketoglutarate-dependent dioxygenase superfamily. Biochemistry. 2004;43:3075-88 pubmed
    ..From comparison of these structures with the crystal structure of AtsK and its complexes, we propose a general mechanism for the catalytic cycle of the alpha-ketoglutarate-dependent dioxygenase superfamily. ..
  49. Lu J, Chai S, Ye Q. Catalysis and inhibition of Mycobacterium tuberculosis methionine aminopeptidase. J Med Chem. 2010;53:1329-37 pubmed publisher
    ..Finally, X-ray structures of MtMetAP1c in complex with three metalloform-selective inhibitors were analyzed, which showed different binding modes and different interactions with metal ions and active site residues. ..
  50. Mikami B, Ban M, Suzuki S, Yoon H, Miyake O, Yamasaki M, et al. Induced-fit motion of a lid loop involved in catalysis in alginate lyase A1-III. Acta Crystallogr D Biol Crystallogr. 2012;68:1207-16 pubmed publisher
    ..In particular, the O(?) atom of Tyr68 in the closed lid loop forms a hydrogen bond to the side chain of a presumed catalytic residue, O(?) of Tyr246, which acts both as an acid and a base catalyst in a syn mechanism. ..
  51. Rodriguez Granillo A, Sedlak E, Wittung Stafshede P. Stability and ATP binding of the nucleotide-binding domain of the Wilson disease protein: effect of the common H1069Q mutation. J Mol Biol. 2008;383:1097-111 pubmed publisher
    ..Taken together, our results provide biophysical characteristics that may be general to N-domains in other P(1B)-ATPases as well as identify changes that may be responsible for the H1069Q WD phenotype in vivo. ..
  52. Tavares G, Panepucci E, Brunger A. Structural characterization of the intramolecular interaction between the SH3 and guanylate kinase domains of PSD-95. Mol Cell. 2001;8:1313-25 pubmed
    ..Based on amino acid conservation and mutational data available in the literature, we propose that this intramolecular interaction is a common feature among MAGUK proteins. ..
  53. Esselborn J, Lambertz C, Adamska Venkates A, Simmons T, Berggren G, Noth J, et al. Spontaneous activation of [FeFe]-hydrogenases by an inorganic [2Fe] active site mimic. Nat Chem Biol. 2013;9:607-609 pubmed publisher
    ..The assembled H-cluster is virtually indistinguishable from the native cofactor. This procedure will be a powerful tool for developing new artificial H?-producing catalysts. ..