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Joseph Wedekind

TitleProfessor
InstitutionSchool of Medicine and Dentistry
DepartmentBiochemistry and Biophysics
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester NY 14642
Other Positions
TitleAssociate Professor
InstitutionUniversity of Rochester Medical Center
DepartmentCancer Center

 
 Awards And Honors
1989     Edmondson Summer Research Fellow  | Dept. of Pathology
1990     Elected Member, Phi Beta Kappa
1992 - 1995NIH Biophysics Training Grant Recipient  | NIH/NIGMS
1995 - 1996Dean's Fellow
1996 - 1999Life Sciences Research Foundation Fellow  | Burroughs Wellcome Fund
1996     Individual NRSA Post-doctoral Fellowship (declined)  | NIH
1996     Leukemia and Lymphoma Society Post-Doctoral Award (declined)  | Leukemia and Lymphoma Society
2005     Faculty Teaching Award in Biophysics  | University of Rochester SMD
2007 - 2009Elected Secretary (The Board of Directors)  | The Pittsburgh Diffraction Society
2010 - 2012Executive Committee Member, CHESS Users' Group  | Cornell High Energy Synchrotron Source, Ithaca NY
2011     Editorial Board Member, The Journal of Biological Chemistry  | ASBMB
 
 Overview
The Wedekind lab investigates the mechanisms of action of non-protein-coding (nc)RNAs. Our goal is to understand the principles by which these molecules gain biological function, which is widely applicable to human disease, as well as the identification of new antimicrobial targets. Model systems include small ribozymes derived from plant viroids, and metabolite sensing riboswitches from bacteria that regulate gene expression. This work is funded by NIH/NIGMS grant R01 GM063162.

We also study the DNA editing enzyme APOBEC3G (A3G), which is an innate anti-HIV-1 factor expressed in CD4+ T cells. Our goal is to elucidate structures of A3G in complex with HIV-1 proteins. Our long-term goal is to develop therapeutics that make A3G more potent in its ability to block viral infectivity. This work is funded by NIH/NIAID grant R33 AI076085.

Our lab primarily employs X-ray crystallography. We greatly acknowledge NIH/NCRR award S10 RR026501 for supporting this instrumentation. For access or further information see: http://dbb.urmc.rochester.edu/bcbp/facilities/bsb_facility.htm

 
 Selected Publications
List All   |   Timeline
  1. Suddala KC, Rinaldi AJ, Feng J, Mustoe AM, Eichhorn CD, Liberman JA, Wedekind JE, Al-Hashimi HM, Brooks CL, Walter NG. Single transcriptional and translational preQ1 riboswitches adopt similar pre-folded ensembles that follow distinct folding pathways into the same ligand-bound structure. Nucleic Acids Res. 2013 Dec 1; 41(22):10462-75.
    View in: PubMed
  2. Can M, Krucinska J, Zoppellaro G, Andersen NH, Wedekind JE, Hersleth HP, Andersson KK, Bren KL. Structural Characterization of Nitrosomonas europaea Cytochrome c-552 Variants with Marked Differences in Electronic Structure. Chembiochem. 2013 Sep 23; 14(14):1828-38.
    View in: PubMed
  3. Liberman JA, Salim M, Krucinska J, Wedekind JE. Structure of a class II preQ1 riboswitch reveals ligand recognition by a new fold. Nat Chem Biol. 2013 Jun; 9(6):353-5.
    View in: PubMed
  4. Wang W, Maucuer A, Gupta A, Manceau V, Thickman KR, Bauer WJ, Kennedy SD, Wedekind JE, Green MR, Kielkopf CL. Structure of Phosphorylated SF1 Bound to U2AF(65) in an Essential Splicing Factor Complex. Structure. 2013 Feb 5; 21(2):197-208.
    View in: PubMed
  5. Salter JD, Lippa GM, Belashov IA, Wedekind JE. Core-Binding Factor ß Increases the Affinity between Human Cullin 5 and HIV-1 Vif within an E3 Ligase Complex. Biochemistry. 2012 Nov 6; 51(44):8702-4.
    View in: PubMed
  6. Banáš P, Sklenovský P, Wedekind JE, Sponer J, Otyepka M. Molecular Mechanism of preQ(1) Riboswitch Action: A Molecular Dynamics Study. J Phys Chem B. 2012 Oct 25; 116(42):12721-34.
    View in: PubMed
  7. Liberman JA, Guo M, Jenkins JL, Krucinska J, Chen Y, Carey PR, Wedekind JE. A Transition-State Interaction Shifts Nucleobase Ionization toward Neutrality To Facilitate Small Ribozyme Catalysis. J Am Chem Soc. 2012 Oct 17; 134(41):16933-6.
    View in: PubMed
  8. Lippa GM, Liberman JA, Jenkins JL, Krucinska J, Salim M, Wedekind JE. Crystallographic analysis of small ribozymes and riboswitches. Methods Mol Biol. 2012; 848:159-84.
    View in: PubMed
  9. Liberman JA, Wedekind JE. Riboswitch structure in the ligand-free state. Wiley Interdiscip Rev RNA. 2012 May-Jun; 3(3):369-84.
    View in: PubMed
  10. Jenkins JL, Krucinska J, McCarty RM, Bandarian V, Wedekind JE. Comparison of a preQ1 riboswitch aptamer in metabolite-bound and free states with implications for gene regulation. J Biol Chem. 2011 Jul 15; 286(28):24626-37.
    View in: PubMed
  11. Liberman JA, Wedekind JE. Base ionization and ligand binding: how small ribozymes and riboswitches gain a foothold in a protein world. Curr Opin Struct Biol. 2011 Jun; 21(3):327-34.
    View in: PubMed
  12. Wedekind JE. Metal ion binding and function in natural and artificial small RNA enzymes from a structural perspective. Met Ions Life Sci. 2011; 9:299-345.
    View in: PubMed
  13. Wedekind JE. The apo riboswitch as a molecular hydra. Structure. 2010 Jul 14; 18(7):757-8.
    View in: PubMed
  14. Salter JD, Krucinska J, Raina J, Smith HC, Wedekind JE. A hydrodynamic analysis of APOBEC3G reveals a monomer-dimer-tetramer self-association that has implications for anti-HIV function. Biochemistry. 2009 Nov 17; 48(45):10685-7.
    View in: PubMed
  15. Guo M, Spitale RC, Volpini R, Krucinska J, Cristalli G, Carey PR, Wedekind JE. Direct Raman measurement of an elevated base pKa in the active site of a small ribozyme in a precatalytic conformation. J Am Chem Soc. 2009 Sep 16; 131(36):12908-9.
    View in: PubMed
  16. Spitale RC, Volpini R, Mungillo MV, Krucinska J, Cristalli G, Wedekind JE. Single-atom imino substitutions at A9 and A10 reveal distinct effects on the fold and function of the hairpin ribozyme catalytic core. Biochemistry. 2009 Aug 25; 48(33):7777-9.
    View in: PubMed
  17. Spitale RC, Wedekind JE. Exploring ribozyme conformational changes with X-ray crystallography. Methods. 2009 Oct; 49(2):87-100.
    View in: PubMed
  18. Spitale RC, Volpini R, Heller MG, Krucinska J, Cristalli G, Wedekind JE. Identification of an imino group indispensable for cleavage by a small ribozyme. J Am Chem Soc. 2009 May 6; 131(17):6093-5.
    View in: PubMed
  19. Spitale RC, Torelli AT, Krucinska J, Bandarian V, Wedekind JE. The structural basis for recognition of the PreQ0 metabolite by an unusually small riboswitch aptamer domain. J Biol Chem. 2009 Apr 24; 284(17):11012-6.
    View in: PubMed
  20. Bennett RP, Salter JD, Liu X, Wedekind JE, Smith HC. APOBEC3G subunits self-associate via the C-terminal deaminase domain. J Biol Chem. 2008 Nov 28; 283(48):33329-36.
    View in: PubMed
  21. MacElrevey C, Salter JD, Krucinska J, Wedekind JE. Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozyme. RNA. 2008 Aug; 14(8):1600-16.
    View in: PubMed
  22. Torelli AT, Spitale RC, Krucinska J, Wedekind JE. Shared traits on the reaction coordinates of ribonuclease and an RNA enzyme. Biochem Biophys Res Commun. 2008 Jun 20; 371(1):154-8.
    View in: PubMed
  23. Jamburuthugoda VK, Santos-Velazquez JM, Skasko M, Operario DJ, Purohit V, Chugh P, Szymanski EA, Wedekind JE, Bambara RA, Kim B. Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. J Biol Chem. 2008 Apr 4; 283(14):9206-16.
    View in: PubMed
  24. Bennett RP, Presnyak V, Wedekind JE, Smith HC. Nuclear Exclusion of the HIV-1 host defense factor APOBEC3G requires a novel cytoplasmic retention signal and is not dependent on RNA binding. J Biol Chem. 2008 Mar 21; 283(12):7320-7.
    View in: PubMed
  25. Spitale RC, Heller MG, Pelly AJ, Wedekind JE. Efficient syntheses of 5'-deoxy-5'-fluoroguanosine and -inosine. J Org Chem. 2007 Oct 26; 72(22):8551-4.
    View in: PubMed
  26. MacElrevey C, Spitale RC, Krucinska J, Wedekind JE. A posteriori design of crystal contacts to improve the X-ray diffraction properties of a small RNA enzyme. Acta Crystallogr D Biol Crystallogr. 2007 Jul; 63(Pt 7):812-25.
    View in: PubMed
  27. Torelli AT, Krucinska J, Wedekind JE. 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 stabilization. RNA. 2007 Jul; 13(7):1052-70.
    View in: PubMed
  28. Lehmann DM, Galloway CA, MacElrevey C, Sowden MP, Wedekind JE, Smith HC. Functional characterization of APOBEC-1 complementation factor phosphorylation sites. Biochim Biophys Acta. 2007 Mar; 1773(3):408-18.
    View in: PubMed
  29. Wedekind JE, Gillilan R, Janda A, Krucinska J, Salter JD, Bennett RP, Raina J, Smith HC. Nanostructures of APOBEC3G support a hierarchical assembly model of high molecular mass ribonucleoprotein particles from dimeric subunits. J Biol Chem. 2006 Dec 15; 281(50):38122-6.
    View in: PubMed
  30. Bennett RP, Diner E, Sowden MP, Lees JA, Wedekind JE, Smith HC. APOBEC-1 and AID are nucleo-cytoplasmic trafficking proteins but APOBEC3G cannot traffic. Biochem Biophys Res Commun. 2006 Nov 10; 350(1):214-9.
    View in: PubMed
  31. Ghosh AK, Sridhar PR, Leshchenko S, Hussain AK, Li J, Kovalevsky AY, Walters DE, Wedekind JE, Grum-Tokars V, Das D, Koh Y, Maeda K, Gatanaga H, Weber IT, Mitsuya H. Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance. J Med Chem. 2006 Aug 24; 49(17):5252-61.
    View in: PubMed
  32. Ichikawa HT, Sowden MP, Torelli AT, Bachl J, Huang P, Dance GS, Marr SH, Robert J, Wedekind JE, Smith HC, Bottaro A. Structural phylogenetic analysis of activation-induced deaminase function. J Immunol. 2006 Jul 1; 177(1):355-61.
    View in: PubMed
  33. Chaves FA, Richards KA, Torelli A, Wedekind J, Sant AJ. Peptide-binding motifs for the I-Ad MHC class II molecule: alternate pH-dependent binding behavior. Biochemistry. 2006 May 23; 45(20):6426-33.
    View in: PubMed
  34. Salter J, Krucinska J, Alam S, Grum-Tokars V, Wedekind JE. Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base variants on the geometry of phosphoryl transfer. Biochemistry. 2006 Jan 24; 45(3):686-700.
    View in: PubMed
  35. MacElrevey C, Wedekind JE. Crystallization and X-ray diffraction analysis of the Trp/amber editing site of hepatitis delta virus (+)RNA: a case of rational design. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Dec 1; 61(Pt 12):1049-53.
    View in: PubMed
  36. Alam S, Grum-Tokars V, Krucinska J, Kundracik ML, Wedekind JE. Conformational heterogeneity at position U37 of an all-RNA hairpin ribozyme with implications for metal binding and the catalytic structure of the S-turn. Biochemistry. 2005 Nov 8; 44(44):14396-408.
    View in: PubMed
  37. Gruswitz F, Frishman M, Goldstein BM, Wedekind JE. Coupling of MBP fusion protein cleavage with sparse matrix crystallization screens to overcome problematic protein solubility. Biotechniques. 2005 Oct; 39(4):476, 478, 480.
    View in: PubMed
  38. Xie K, Song SC, Spitalnik SL, Wedekind JE. Crystallographic analysis of the NNA7 Fab and proposal for the mode of human blood-group recognition. Acta Crystallogr D Biol Crystallogr. 2005 Oct; 61(Pt 10):1386-94.
    View in: PubMed
  39. Jamburuthugoda VK, Guo D, Wedekind JE, Kim B. Kinetic evidence for interaction of human immunodeficiency virus type 1 reverse transcriptase with the 3'-OH of the incoming dTTP substrate. Biochemistry. 2005 Aug 9; 44(31):10635-43.
    View in: PubMed
  40. Goodman JL, Wang S, Alam S, Ruzicka FJ, Frey PA, Wedekind JE. Ornithine cyclodeaminase: structure, mechanism of action, and implications for the mu-crystallin family. Biochemistry. 2004 Nov 9; 43(44):13883-91.
    View in: PubMed
  41. Smith HC, Bottaro A, Sowden MP, Wedekind JE. Activation induced deaminase: the importance of being specific. Trends Genet. 2004 Jun; 20(6):224-7.
    View in: PubMed
  42. Xie K, Sowden MP, Dance GS, Torelli AT, Smith HC, Wedekind JE. The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBEC-1. Proc Natl Acad Sci U S A. 2004 May 25; 101(21):8114-9.
    View in: PubMed
  43. Alam S, Wang SC, Ruzicka FJ, Frey PA, Wedekind JE. Crystallization and X-ray diffraction analysis of ornithine cyclodeaminase from Pseudomonas putida. Acta Crystallogr D Biol Crystallogr. 2004 May; 60(Pt 5):941-4.
    View in: PubMed
  44. Song SC, Xie K, Czerwinski M, Spitalnik SL, Wedekind JE. Purification, crystallization and X-ray diffraction analysis of a recombinant Fab that recognizes a human blood-group antigen. Acta Crystallogr D Biol Crystallogr. 2004 Apr; 60(Pt 4):788-91.
    View in: PubMed
  45. Wedekind JE, McKay DB. Crystal structure of the leadzyme at 1.8 A resolution: metal ion binding and the implications for catalytic mechanism and allo site ion regulation. Biochemistry. 2003 Aug 19; 42(32):9554-63.
    View in: PubMed
  46. Wedekind JE, Dance GS, Sowden MP, Smith HC. Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business. Trends Genet. 2003 Apr; 19(4):207-16.
    View in: PubMed
  47. Grum-Tokars V, Milovanovic M, Wedekind JE. Crystallization and X-ray diffraction analysis of an all-RNA U39C mutant of the minimal hairpin ribozyme. Acta Crystallogr D Biol Crystallogr. 2003 Jan; 59(Pt 1):142-5.
    View in: PubMed
  48. Wedekind JE, Trame CB, Dorywalska M, Koehl P, Raschke TM, McKee M, FitzGerald D, Collier RJ, McKay DB. Refined crystallographic structure of Pseudomonas aeruginosa exotoxin A and its implications for the molecular mechanism of toxicity. J Mol Biol. 2001 Dec 7; 314(4):823-37.
    View in: PubMed
  49. Wedekind JE, McKay DB. Purification, crystallization, and X-ray diffraction analysis of small ribozymes. Methods Enzymol. 2000; 317:149-68.
    View in: PubMed
  50. Wedekind JE, McKay DB. Crystal structure of a lead-dependent ribozyme revealing metal binding sites relevant to catalysis. Nat Struct Biol. 1999 Mar; 6(3):261-8.
    View in: PubMed
  51. Wedekind JE, McKay DB. Crystallographic structures of the hammerhead ribozyme: relationship to ribozyme folding and catalysis. Annu Rev Biophys Biomol Struct. 1998; 27:475-502.
    View in: PubMed
  52. Babbitt PC, Hasson MS, Wedekind JE, Palmer DR, Barrett WC, Reed GH, Rayment I, Ringe D, Kenyon GL, Gerlt JA. The enolase superfamily: a general strategy for enzyme-catalyzed abstraction of the alpha-protons of carboxylic acids. Biochemistry. 1996 Dec 24; 35(51):16489-501.
    View in: PubMed
  53. Reed GH, Poyner RR, Larsen TM, Wedekind JE, Rayment I. Structural and mechanistic studies of enolase. Curr Opin Struct Biol. 1996 Dec; 6(6):736-43.
    View in: PubMed
  54. Wedekind JE, Frey PA, Rayment I. The structure of nucleotidylated histidine-166 of galactose-1-phosphate uridylyltransferase provides insight into phosphoryl group transfer. Biochemistry. 1996 Sep 10; 35(36):11560-9.
    View in: PubMed
  55. Larsen TM, Wedekind JE, Rayment I, Reed GH. A carboxylate oxygen of the substrate bridges the magnesium ions at the active site of enolase: structure of the yeast enzyme complexed with the equilibrium mixture of 2-phosphoglycerate and phosphoenolpyruvate at 1.8 A resolution. Biochemistry. 1996 Apr 9; 35(14):4349-58.
    View in: PubMed
  56. Wedekind JE, Frey PA, Rayment I. Three-dimensional structure of galactose-1-phosphate uridylyltransferase from Escherichia coli at 1.8 A resolution. Biochemistry. 1995 Sep 5; 34(35):11049-61.
    View in: PubMed
  57. Ruzicka FJ, Wedekind JE, Kim J, Rayment I, Frey PA. Galactose-1-phosphate uridylyltransferase from Escherichia coli, a zinc and iron metalloenzyme. Biochemistry. 1995 Apr 25; 34(16):5610-7.
    View in: PubMed
  58. Wedekind JE, Reed GH, Rayment I. Octahedral coordination at the high-affinity metal site in enolase: crystallographic analysis of the MgII--enzyme complex from yeast at 1.9 A resolution. Biochemistry. 1995 Apr 4; 34(13):4325-30.
    View in: PubMed
  59. Wedekind JE, Poyner RR, Reed GH, Rayment I. Chelation of serine 39 to Mg2+ latches a gate at the active site of enolase: structure of the bis(Mg2+) complex of yeast enolase and the intermediate analog phosphonoacetohydroxamate at 2.1-A resolution. Biochemistry. 1994 Aug 9; 33(31):9333-42.
    View in: PubMed
  60. Wedekind JE, Frey PA, Rayment I. Crystallization and preliminary crystallographic analysis of galactose-1-phosphate uridylyltransferase from Escherichia coli. Acta Crystallogr D Biol Crystallogr. 1994 May 1; 50(Pt 3):329-31.
    View in: PubMed

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