Research Topics
Genomes and Genes
| Joseph E WedekindSummaryAffiliation: University of Rochester Country: USA Publications
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Detail Information
Publications
Nanostructures of APOBEC3G support a hierarchical assembly model of high molecular mass ribonucleoprotein particles from dimeric subunitsJoseph E Wedekind
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
J Biol Chem 281:38122-6. 2006..These observations imply that the disruption of cellular HMM particles may require regulation of protein-RNA, as well as protein-protein interactions, which has implications for therapeutic development...
APOBEC3G subunits self-associate via the C-terminal deaminase domainRyan P Bennett
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 283:33329-36. 2008..These findings corroborate the small angle x-ray scattering structural model and are instructive for development of high throughput screens that target specific domains and their functions to identify HIV/AIDS therapeutics...
Shared traits on the reaction coordinates of ribonuclease and an RNA enzymeAndrew T Torelli
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue Box 712, Rochester, New York 14642, USA
Biochem Biophys Res Commun 371:154-8. 2008..The advantages of 2',5'-linkages to investigate phosphoryl-transfer reactions are discussed, and argue for their expanded use in structural studies...
Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozymeCeleste MacElrevey
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
RNA 14:1600-16. 2008..These findings demonstrate the importance of the Ade38 Watson-Crick face in attaining a reaction-intermediate state and the sensitivity of the RNA fold to restructuring when electrostatic and shape features fail to complement...
The structural basis for recognition of the PreQ0 metabolite by an unusually small riboswitch aptamer domainRobert C Spitale
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 284:11012-6. 2009..The structure offers insight into the mode of ribosome-binding site sequestration by a minimal RNA fold stabilized by metabolite binding and has implications for understanding the molecular basis by which bacterial genes are regulated...
Identification of an imino group indispensable for cleavage by a small ribozymeRobert C Spitale
Department of Chemistry, University of Rochester, RC Box 270216, Rochester, New York 14627 0216, USA
J Am Chem Soc 131:6093-5. 2009..This work demonstrates the efficacy of single-atom approaches in the analysis of ncRNA structure-function relationships...
Exploring ribozyme conformational changes with X-ray crystallographyRobert C Spitale
Department of Chemistry, Biological Chemistry Cluster, Rochester, NY 14627 0216, USA
Methods 49:87-100. 2009..The methods are broadly applicable to other RNA systems...
Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base variants on the geometry of phosphoryl transferJason Salter
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
Biochemistry 45:686-700. 2006..Finally, the results indicated that ordered water molecules bind near the 2'-hydroxyl of A-1, lending support to the hypothesis that solvent may play an important role in the reaction...
Nuclear Exclusion of the HIV-1 host defense factor APOBEC3G requires a novel cytoplasmic retention signal and is not dependent on RNA bindingRyan P Bennett
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 283:7320-7. 2008..The CRS lies in a region involved in both Gag and Vif interactions; therefore, identification of this motif has important implications for the design of therapeutics that target HIV-1 while maintaining antiviral and cellular functions...
Structural phylogenetic analysis of activation-induced deaminase functionH Travis Ichikawa
Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
J Immunol 177:355-61. 2006....
APOBEC-1 and AID are nucleo-cytoplasmic trafficking proteins but APOBEC3G cannot trafficRyan P Bennett
Department of Biochemistry, Box 712, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
Biochem Biophys Res Commun 350:214-9. 2006..We demonstrate that hA3G is not a nucleo-cytoplasmic shuttling protein like APOBEC-1 and AID, but is strongly retained in the cytoplasm through a mechanism that involves both the N and C-terminal regions of the protein...
A posteriori design of crystal contacts to improve the X-ray diffraction properties of a small RNA enzymeCeleste MacElrevey
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
Acta Crystallogr D Biol Crystallogr 63:812-25. 2007..The results demonstrate how knowledge-based design can be used to improve diffraction and overcome otherwise destabilizing defects...
A comparison of vanadate to a 2'-5' linkage at the active site of a small ribozyme suggests a role for water in transition-state stabilizationAndrew T Torelli
Department of Biochemistry and Biophysics, Rochester, NY 14642, USA
RNA 13:1052-70. 2007..Such coordination has not been reported for small ribozymes, but is consistent with the structures of protein enzymes. Overall, this work establishes significant parallels between the RNA and protein enzyme worlds...
Riboswitch structure in the ligand-free stateJoseph A Liberman
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
Wiley Interdiscip Rev RNA 3:369-84. 2012..An understanding of these topics is essential to comprehend riboswitch gene regulation at the molecular level, which has already provided a basis to understand the mechanism of action of natural antimicrobials...
Functional characterization of APOBEC-1 complementation factor phosphorylation sitesDavid M Lehmann
Environmental Health Sciences Center, Department of Toxicology, University of Rochester, Rochester, NY 14642, USA
Biochim Biophys Acta 1773:408-18. 2007..These data suggest that phosphorylation of ACF by PKC may be a key regulatory mechanism of apoB mRNA editing in rat hepatocytes...
A hydrodynamic analysis of APOBEC3G reveals a monomer-dimer-tetramer self-association that has implications for anti-HIV functionJason D Salter
Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA
Biochemistry 48:10685-7. 2009..Overall, the results provide physical restraints for the A3G quaternary structure that have implications for modulating antiviral function...
Single-atom imino substitutions at A9 and A10 reveal distinct effects on the fold and function of the hairpin ribozyme catalytic coreRobert C Spitale
Department of Biochemistry and Biophysics, 601 Elmwood Avenue, Box 712, Rochester New York 14642, USA
Biochemistry 48:7777-9. 2009..We propose that the imino moiety of A9 promotes a key water-mediated contact that favors transition-state formation, which suggests an enhanced chemical repertoire for RNA...
The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBEC-1Kefang Xie
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Proc Natl Acad Sci U S A 101:8114-9. 2004..Most importantly, the results suggested both AID and APOBEC-1 are equally likely to bind single-stranded DNA or RNA, which has implications for the identification of natural AID targets...
Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophageVaruni K Jamburuthugoda
Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Biol Chem 283:9206-16. 2008..This can restrict ground state dNTP binding and lead to inefficient DNA synthesis particularly at low dNTP concentrations, ultimately contributing to viral replication failure in macrophage and instability in vivo of the M184I mutation...
Crystallographic analysis of the NNA7 Fab and proposal for the mode of human blood-group recognitionKefang Xie
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Acta Crystallogr D Biol Crystallogr 61:1386-94. 2005..These results suggest a model for recognition of the glycopeptide antigen that accounts for the deleterious effect of the G91S substitution...
Comparison of a preQ1 riboswitch aptamer in metabolite-bound and free states with implications for gene regulationJermaine L Jenkins
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 286:24626-37. 2011..These observations are distinct from transcriptional preQ(1) riboswitches of the same class that exhibit strictly ligand-dependent folding. Implications for gene regulation are discussed...
Ornithine cyclodeaminase: structure, mechanism of action, and implications for the mu-crystallin familyJessica L Goodman
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Box 712, Rochester, New York 14642, USA
Biochemistry 43:13883-91. 2004..A more parsimonious description of the chemical mechanism is proposed and discussed in relation to the structure and function of mu-crystallins...
Crystallization and X-ray diffraction analysis of the Trp/amber editing site of hepatitis delta virus (+)RNA: a case of rational designCeleste MacElrevey
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
Acta Crystallograph Sect F Struct Biol Cryst Commun 61:1049-53. 2005..5, c = 63.5 A. The crystallization and X-ray analysis of multiple forms of the HDV RNA-editing substrate, encounters with common RNA crystal-growth defects and a strategy to overcome these problems are reported...
Base ionization and ligand binding: how small ribozymes and riboswitches gain a foothold in a protein worldJoseph A Liberman
Department of Biochemistry and Biophysics, and Center for RNA Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States
Curr Opin Struct Biol 21:327-34. 2011..The results showcase the breadth of functionality attainable from ncRNAs, as well as molecular features notable for antibacterial design...
A transition-state interaction shifts nucleobase ionization toward neutrality to facilitate small ribozyme catalysisJoseph A Liberman
Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA
J Am Chem Soc 134:16933-6. 2012..Overall the results quantify the contribution of a single electrostatic interaction to base ionization, which has broad relevance for understanding how RNA structure can control chemical reactivity...
Crystallographic analysis of small ribozymes and riboswitchesGeoffrey M Lippa
Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY, USA
Methods Mol Biol 848:159-84. 2012..The methods presented provide a guide for comparable investigations of noncoding RNA molecules including a 48-solution, "first choice" RNA crystal screen compiled from our prior successes with commercially available screens...
Metal ion binding and function in natural and artificial small RNA enzymes from a structural perspectiveJoseph E Wedekind
Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Met Ions Life Sci 9:299-345. 2011..When metal ion binding isn't possible, ribozymes make due by ionizing their bases, or by recruiting cofactors that augment their chemical functionality...
Activation induced deaminase: the importance of being specificHarold C Smith
Department of Biochemistry and Biophysics, The James P Wilmot Cancer Center, USA
Trends Genet 20:224-7. 2004..Recently, the biological relevance of assaying mammalian enzymes for DNA deaminase activity using Escherichia coli DNA as a reporter has been questioned, representing another round in the ongoing debate...
Conformational heterogeneity at position U37 of an all-RNA hairpin ribozyme with implications for metal binding and the catalytic structure of the S-turnShabnam Alam
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
Biochemistry 44:14396-408. 2005..A comparison of all three new structures has implications for the catalytically relevant conformation of the S-turn and suggests a rationale for the distinctive metal dependence of each mutant...
Core-binding factor β increases the affinity between human Cullin 5 and HIV-1 Vif within an E3 ligase complexJason D Salter
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, United States
Biochemistry 51:8702-4. 2012..An additional interface between Cul5 and an N-terminal region of Vif appears to be plausible, which has therapeutic design implications...
Efficient syntheses of 5'-deoxy-5'-fluoroguanosine and -inosineRobert C Spitale
Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA
J Org Chem 72:8551-4. 2007....
Coupling of MBP fusion protein cleavage with sparse matrix crystallization screens to overcome problematic protein solubilityFranz Gruswitz
University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Biotechniques 39:476, 478, 480. 2005
Kinetic evidence for interaction of human immunodeficiency virus type 1 reverse transcriptase with the 3'-OH of the incoming dTTP substrateVaruni K Jamburuthugoda
Department of Biochemistry and Biophysics, University of Rochester, 601 Elmwood Avenue, Box 672, Rochester, New York 14642, USA
Biochemistry 44:10635-43. 2005..The kinetic data presented in this report demonstrate the functional role of the Q151 residue in HIV-1 RT interaction with dTTP and its analogues containing chemical modifications at the 3'-C of the sugar moiety...
Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family businessJoseph E Wedekind
Department of Biochemistry and Biophysics, University of Rochester, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14623, USA
Trends Genet 19:207-16. 2003..In light of the hypothesis that these proteins might represent novel mRNA editing systems that could affect proteome diversity, we consider their structure, expression and relevance to biomedically significant processes or pathologies...
