STRUCTURAL MOLECULAR BIOLOGY AND PROTEIN DESIGN

John A. Tainer, Ph.D.

Professor, Department of Molecular Biology
and The Skaggs Institute for Chemical Biology
J. A. Tainer, M. Aoyagi, A. S. Arvai, J.-L. Bodmer, D. P. Barondeau, R. M. Brudler, J. M. Castagnetto, B. R. Chapados, L. Craig, T. H. Cross, D. S. Daniels, M. Didonato, G. DiVita, L. Fan, E. D. Garcin, S. W. Hennessy, K. Hitomi, C. J. Kassman, S. J. Loyd, C. D. Mol, G. Moncalian, J.J. Perry, M. E. Pique, D. S. Shin, R. S. Williams, M. M. Thayer, T. T. Woo, T. I. Wood
[Recent Graduates] [Former members]

Other Useful Information: Grant Deadlines, Synchroton Deadlines

Key words: DNA-repair, metalloenzyme, oxidative damage, degenerative disease, infectious disease, Lou Gehrig's disease, superoxide dismutase, cell cycle, cancer, protein design

IMMEDIATE OPENING - SEEKING BIOCHEMIST/MOLECULAR BIOLOGIST. 
SEEKING MACROMOLECULAR CRYSTALLOGRAPHERS - Positions Available. 

Visit some of our collaborators at TSRI: [E. D. Getzoff] [V. A. Roberts][Metalloprotein Structure and Design Group]

Internal Pages: [Beamline Phone Numbers]

Movie of reaction AP Endonuclease DNA repair enzyme

( Click to see the movie ) 

DNA Damage Excision Enzyme Structures

(Click to see larger image)



 

Structure of Nitric Oxide Synthase Oxygenase Dimer with Pterin and Substrate.

B.R. Crane, A.S. Arvai, D.K. Ghosh, C. Wu, E.D. Getzoff, D.J. Stuehr and J.A. Tainer.

Science 279, 2121-21216, 1998. Visit Science Magazine Online

Check out our NOS Steroeviews and Figures.

We focus on four classes of proteins that interface structural biology with cellular chemistry:

  1. Enzymes regulating reactive oxygen and xenotoxin control (superoxide dismutases, catalase, and glutathione transferase);
  2. Enzymes controlling DNA repair and evolution enzymes;
  3. Pilus fiber motility and adherence proteins for bacterial pathogens;
  4. Cell cycle control proteins.
Current structural and design results are contributing to an understanding of these systems that should contribute to new treatments for infectious disease, degenerative diseases, and cancer.

Bacterial pilus structure, assembly, and antigenicity.

We seek to improve understanding and to develop new treatments for the many bacterial pathogens that use long fibers termed Type IV pili for attachment and mobility. We solved the crystallographic structure of the pilus fiber- forming pilin protein essential to the virulence of these pathogens, which includes Neisseria meningitidis, Neisseria gonorrhoeae, Pseudomonas aeroginosa, Dichlobacter nodosus, Moraxella bovis, Vibrio cholerae, and enterotoxogenic Escherichia coli. The pilin subunit is ladle- shaped with an extended a-helix spine wrapped at one end by b-sheet. A few key residue interactions allow the remaining part of a hypervariable region to undergo extreme antigenic variation to escape t he host immune response. The assembled fiber shows extreme sequence variation plus glycosylation and phosphorylation at the survace. However, we have defined two conserved regions recognized by human, mouse, and rabbit antibodies. Current efforts include the redesign of pilin to develop potential vaccines by replacing the hypervariable region with epitopes from other essential target proteins. 

Reactive oxygen and xenobiotic control enzymes.

Atomic structures of human cytoplasmic Cu,Zn superoxide dismutases, the mitochondrial Mn superoxide dismutases, and schistosomal glutathione transferases are improving our understanding of reactive oxygen and xenobiotic control within cells. Superoxide dismutases (SODs) are master regulators for reactive oxygen species involved in injury, pathogenesis, aging and degenerative diseases. For Cu,Zn SOD, we have defined the active site structural chemistry responsible for the rapid reaction. We are now exam ining how single site mutations cause degenerative disease such as Lou Gehrig's disease or familial amyotrophic lateral sclerosis (FALS). For Mn SOD, single site mutations can destabilize the tetramer and also reduce stability and activity in ways that ma y cause degenerative diseases. Structures of glutathione-S-transferase (GST), which is an essential detoxification enzyme in all organisms, show how the leading anti-schistosomal drug praziquantel binds to GST. This information may allow the design of new drugs to overcome the growing resistance to current schistosomal drugs. Protein design on GST enzymes includes using random libraries for the loop regions surrounding the active site, thereby developing glubodies as a new class of binding proteins in bio technology. 

DNA-repair and genetic evolution.

Cells must balance DNA repair to preserve fidelity with DNA variation allowing evolutionary changes. As over 10,000 DNA bases per day are repaired in each human cell, DNA excision-repair enzymes are essential to cell survival and to protection against cancer-causing mutations. Surprisingly, DNA repair inhibitors may improve current radiation and chemotherapies for cancer by specifically killing cancer cells which unlike normal cells will often undergo DNA synthesis and cell division with unrepaired DNA resulting in their death. Our DNA repair enzyme structures show how damaged DNA bases are recognized and removed in atomic detail. These enzymes repair DNA by flipping the DNA nucleotides out from the double helix and into specific binding pockets (Figure), which are ideal for the design of inhibitors for anti-cancer therapies. We confirmed our understanding of these binding pockets by deliberately altering the specificity of the DNA repair enzyme uracil-DNA glycosylase to remove cytosine or thymine from normal DNA resulting in mutator phenotypes in vivo. We found that the endonuclease III structure is representative of a superfamily of DNA repair enzymes and a key HhH motif that recognizes DNA backbone. Our new structure of the major DNA-repair APendonuclease, which cuts DNA at sites where bases are missing, defines its active site and identifies mechanism for recognizing missing bases.

Human dUTP pyrophosphatase (dUTPase) catalyzes the breakdown of uracil nucleotide triphosphates to keep the RNA base uracil out of DNA and to provide material for the biosynthesis of the DNA building block dTTP. These dUTPase functions prevent thymic-less cell death from cycles of uracil misincorporation and removal that would generate multiple DNA strand breaks and eventual cell death. Atomic structures of dUTPase with bound nucleotides reveal uracil binds within a groove that is then capped when the flexible tail region closes over the bound dUTP substrate. These structures establish how dUTPase recognizes its substrate with exquisite specificity and provide a basis for the design of inhibitors as future anti-cancer drugs.

Cell cycle control.

Together with Steve Reed's group, we are working to define structural controls on cell cycle progression. Structures of the Cks or suc1 proteins which are essential to cell cycle progression, provide clues for new mechanisms for cell cycle regulation via a conformational switch that controls two distinct Cks folds and assemblies. A straight b-hinge conformation of Cks, which forms a dimer of swapped b-strands blocks binding to the cell cycle kinase Cdk2. Formation of a closed, bent b- hinge conformation creates a single domain fold that promotes Cdk2 binding (Figure). Preliminary experiments by Steve Reed's group show that blocking Cks expression results in cell death for several types of cancer cells suggesting this is a useful cancer drug target.

Publications

  1. Putnam CD, Clancy SB, Tsuruta H, Gonzalez S, Wetmur JG, Tainer JA Structure and mechanism of the RuvB Holliday junction branch migrati J Mol Biol. 2001 Aug 10;311(2):297-310.

    2.  
  2. Chung JH, Suh MJ, Park YI, Tainer JA, Han YS. Repair activities of 8-oxoguanine DNA glycosylase from Archaeoglobus hyperthermophilic archaeon. Mutat Res. 2001 Jul 12;486(2):99-111.

    3.  
  3. Hopfner KP, Karcher A, Craig L, Woo TT, Carney JP, Tainer JA. Structural biochemistry and interaction architecture of the DNA doub break repair Mre11 nuclease and Rad50-ATPase. Cell. 2001 May 18;105(4):473-85.

    4.  
  4. Ayala BP, Vasquez B, Clary S, Tainer JA, Rodland K, So M. The pilus-induced Ca2+ flux triggers lysosome exocytosis and increas amount of Lamp1 accessible to Neisseria IgA1 protease. Cell Microbiol. 2001 Apr;3(4):265-75.

    5.  
  5. Chapados BR, Chai Q, Hosfield DJ, Qiu J, Shen B, Tainer JA. Structural biochemistry of a type 2 RNase H: RNA primer recognition during DNA replication. J Mol Biol. 2001 Mar 23;307(2):541-56.

    6.  
  6. Hopfner KP, Tainer JA. DNA mismatch repair: the hands of a genome guardian. Structure Fold Des. 2000 Dec 15;8(12):R237-41. Review.

    7.  
  7. Han S, Arvai AS, Clancy SB, Tainer JA. Crystal structure and novel recognition motif of rho ADP-ribosylatin exoenzyme from Clostridium botulinum: structural insights for recogn specificity and catalysis. J Mol Biol. 2001 Jan 5;305(1):95-107.

    8.  
  8. Hopfner KP, Karcher A, Shin D, Fairley C, Tainer JA, Carney JP. Mre11 and Rad50 from Pyrococcus furiosus: cloning and biochemical characterization reveal an evolutionarily conserved multiprotein mac J Bacteriol. 2000 Nov;182(21):6036-41.

    9.  
  9. Bourne Y, Watson MH, Arvai AS, Bernstein SL, Reed SI, Tainer JA. Crystal structure and mutational analysis of the Saccharomyces cerev cycle regulatory protein Cks1: implications for domain swapping, ani and protein interactions. Structure Fold Des. 2000 Aug 15;8(8):841-50.

    10.  
  10. Mol CD, Hosfield DJ, Tainer JA. Abasic site recognition by two apurinic/apyrimidinic endonuclease fa DNA base excision repair: the 3' ends justify the means. Mutat Res. 2000 Aug 30;460(3-4):211-29. Review.

    11.  
  11. Parikh SS, Putnam CD, Tainer JA. Lessons learned from structural results on uracil-DNA glycosylase. Mutat Res. 2000 Aug 30;460(3-4):183-99. Review.

    12.  
  12. Daniels DS, Tainer JA. Conserved structural motifs governing the stoichiometric repair of a by O(6)-alkylguanine-DNA alkyltransferase. Mutat Res. 2000 Aug 30;460(3-4):151-63. Review.

    13.  
  13. Tainer JA, Friedberg EC. Dancing with the elephants: envisioning the structural biology of DN pathways. Mutat Res. 2000 Aug 30;460(3-4):139-41. No abstract available.

    14.  
  14. Hopfner KP, Karcher A, Shin DS, Craig L, Arthur LM, Carney JP, T Structural biology of Rad50 ATPase: ATP-driven conformational contro double-strand break repair and the ABC-ATPase superfamily. Cell. 2000 Jun 23;101(7):789-800.

    15.  
  15. Leveque VJ, Stroupe ME, Lepock JR, Cabelli DE, Tainer JA, Nick H DN. Multiple replacements of glutamine 143 in human manganese superoxide effects on structure, stability, and catalysis. Biochemistry. 2000 Jun 20;39(24):7131-7.

    16.  
  16. Parikh SS, Walcher G, Jones GD, Slupphaug G, Krokan HE, Blackbur JA. Uracil-DNA glycosylase-DNA substrate and product structures: conform strain promotes catalytic efficiency by coupled stereoelectronic eff Proc Natl Acad Sci U S A. 2000 May 9;97(10):5083-8.

    17.  
  17. Koc ON, Gerson SL, Cooper BW, Laughlin M, Meyerson H, Kutteh L, Szekely EM, Tainer N, Lazarus HM. Randomized cross-over trial of progenitor-cell mobilization: high-do cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) granulocyte-macrophage colony-stimulating factor plus G-CSF. J Clin Oncol. 2000 May;18(9):1824-30.

    18.  
  18. Crane BR, Arvai AS, Ghosh S, Getzoff ED, Stuehr DJ, Tainer JA. Structures of the N(omega)-hydroxy-L-arginine complex of inducible n synthase oxygenase dimer with active and inactive pterins. Biochemistry. 2000 Apr 25;39(16):4608-21.

    19.  
  19. Daniels DS, Mol CD, Arvai AS, Kanugula S, Pegg AE, Tainer JA. Active and alkylated human AGT structures: a novel zinc site, inhibi extrahelical base binding. EMBO J. 2000 Apr 3;19(7):1719-30.

    20.  
  20. Zu JS, Deng HX, Lo TP, Mitsumoto H, Ahmed MS, Hung WY, Cai ZJ, T Siddique T. Exon 5 encoded domain is not required for the toxic function of muta essential for the dismutase activity: identification and characteriz new SOD1 mutations associated with familial amyotrophic lateral scle Neurogenetics. 1997 May;1(1):65-71.

    21.  
  21. Mol CD, Izumi T, Mitra S, Tainer JA. DNA-bound structures and mutants reveal abasic DNA binding by APE1 a repair coordination [corrected] Nature. 2000 Jan 27;403(6768):451-6.

    22.  
  22. Putnam CD, Arvai AS, Bourne Y, Tainer JA. Active and inhibited human catalase structures: ligand and NADPH bin catalytic mechanism. J Mol Biol. 2000 Feb 11;296(1):295-309.

    23.  
  23. Putnam CD, Tainer JA. The food of sweet and bitter fancy. Nat Struct Biol. 2000 Jan;7(1):17-8.

    24.  
  24. Crane BR, Rosenfeld RJ, Arvai AS, Ghosh DK, Ghosh S, Tainer JA, Getzoff ED. N-terminal domain swapping and metal ion binding in nitric oxide syn dimerization. EMBO J. 1999 Nov 15;18(22):6271-81.

    25.  
  25. Ghosh DK, Crane BR, Ghosh S, Wolan D, Gachhui R, Crooks C, Prest JA, Getzoff ED, Stuehr DJ. Inducible nitric oxide synthase: role of the N-terminal beta-hairpin pterin-binding segment in dimerization and tetrahydrobiopterin inter EMBO J. 1999 Nov 15;18(22):6260-70.

    26.  
  26. Cabelli DE, Guan Y, Leveque V, Hearn AS, Tainer JA, Nick HS, Sil Role of tryptophan 161 in catalysis by human manganese superoxide di Biochemistry. 1999 Sep 7;38(36):11686-92.

    27.  
  27. Han S, Craig JA, Putnam CD, Carozzi NB, Tainer JA. Evolution and mechanism from structures of an ADP-ribosylating toxin complex. Nat Struct Biol. 1999 Oct;6(10):932-6.

    28.  
  28. Ramilo CA, Leveque V, Guan Y, Lepock JR, Tainer JA, Nick HS, Sil Interrupting the hydrogen bond network at the active site of human m superoxide dismutase. J Biol Chem. 1999 Sep 24;274(39):27711-6.

    29.  
  29. Adak S, Crooks C, Wang Q, Crane BR, Tainer JA, Getzoff ED, Stueh Tryptophan 409 controls the activity of neuronal nitric-oxide syntha regulating nitric oxide feedback inhibition. J Biol Chem. 1999 Sep 17;274(38):26907-11.

    30.  
  30. Hosfield DJ, Guan Y, Haas BJ, Cunningham RP, Tainer JA. Structure of the DNA repair enzyme endonuclease IV and its DNA compl double-nucleotide flipping at abasic sites and three-metal-ion catal Cell. 1999 Aug 6;98(3):397-408.

    31.  
  31. Ghosh S, Wolan D, Adak S, Crane BR, Kwon NS, Tainer JA, Getzoff DJ. Mutational analysis of the tetrahydrobiopterin-binding site in induc nitric-oxide synthase. J Biol Chem. 1999 Aug 20;274(34):24100-12.

    32.  
  32. Pellequer JL, Chen Sw, Roberts VA, Tainer JA, Getzoff ED. Unraveling the effect of changes in conformation and compactness at V(L)-V(H) interface upon antigen binding. J Mol Recognit. 1999 Jul-Aug;12(4):267-75.

    33.  
  33. Mol CD, Parikh SS, Putnam CD, Lo TP, Tainer JA. DNA repair mechanisms for the recognition and removal of damaged DNA Annu Rev Biophys Biomol Struct. 1999;28:101-28. Review.

    34.  
  34. Bruns CM, Hubatsch I, Ridderstrom M, Mannervik B, Tainer JA. Human glutathione transferase A4-4 crystal structures and mutagenesi basis of high catalytic efficiency with toxic lipid peroxidation pro J Mol Biol. 1999 May 7;288(3):427-39.

    35.  
  35. Haas BJ, Sandigursky M, Tainer JA, Franklin WA, Cunningham RP. Purification and characterization of Thermotoga maritima endonucleas thermostable apurinic/apyrimidinic endonuclease and 3'-repair dieste J Bacteriol. 1999 May;181(9):2834-9.

    36.  
  36. Shroyer MJ, Bennett SE, Putnam CD, Tainer JA, Mosbaugh DW. Mutation of an active site residue in Escherichia coli uracil-DNA gl effect on DNA binding, uracil inhibition and catalysis. Biochemistry. 1999 Apr 13;38(15):4834-45.

    37.  
  37. Putnam CD, Shroyer MJ, Lundquist AJ, Mol CD, Arvai AS, Mosbaugh JA. Protein mimicry of DNA from crystal structures of the uracil-DNA gly inhibitor protein and its complex with Escherichia coli uracil-DNA g J Mol Biol. 1999 Mar 26;287(2):331-46.

    38.  
  38. Forest KT, Dunham SA, Koomey M, Tainer JA. Crystallographic structure reveals phosphorylated pilin from Neisser phosphoserine sites modify type IV pilus surface chemistry and fibre Mol Microbiol. 1999 Feb;31(3):743-52.

    39.  
  39. Parikh SS, Mol CD, Hosfield DJ, Tainer JA. Envisioning the molecular choreography of DNA base excision repair. Curr Opin Struct Biol. 1999 Feb;9(1):37-47. Review.

    40.  
  40. Guan Y, Manuel RC, Arvai AS, Parikh SS, Mol CD, Miller JH, Lloyd JA. MutY catalytic core, mutant and bound adenine structures define spec DNA repair enzyme superfamily. Nat Struct Biol. 1998 Dec;5(12):1058-64.

    41.  
  41. Hosfield DJ, Mol CD, Shen B, Tainer JA. Structure of the DNA repair and replication endonuclease and exonucl coupling DNA and PCNA binding to FEN-1 activity. Cell. 1998 Oct 2;95(1):135-46.

    42.  
  42. Hosfield DJ, Frank G, Weng Y, Tainer JA, Shen B. Newly discovered archaebacterial flap endonucleases show a structure mechanism for DNA substrate binding and catalysis resembling human f endonuclease-1. J Biol Chem. 1998 Oct 16;273(42):27154-61.

    43.  
  43. Coombs GS, Bergstrom RC, Pellequer JL, Baker SI, Navre M, Smith JA, Madison EL, Corey DR. Substrate specificity of prostate-specific antigen (PSA). Chem Biol. 1998 Sep;5(9):475-88.

    44.  
  44. Schnecke V, Swanson CA, Getzoff ED, Tainer JA, Kuhn LA. Screening a peptidyl database for potential ligands to proteins with flexibility. Proteins. 1998 Oct 1;33(1):74-87.

    45.  
  45. Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA. Base excision repair initiation revealed by crystal structures and b kinetics of human uracil-DNA glycosylase with DNA. EMBO J. 1998 Sep 1;17(17):5214-26.

    46.  
  46. Shen B, Qiu J, Hosfield D, Tainer JA. Flap endonuclease homologs in archaebacteria exist as independent pr Trends Biochem Sci. 1998 May;23(5):171-3. Review. No abstract availa

    47.  
  47. Tong W, Burdi D, Riggs-Gelasco P, Chen S, Edmondson D, Huynh BH, Han S, Arvai A, Tainer J. Characterization of Y122F R2 of Escherichia coli ribonucleotide redu time-resolved physical biochemical methods and X-ray crystallography Biochemistry. 1998 Apr 28;37(17):5840-8.

    48.  
  48. Hsieh Y, Guan Y, Tu C, Bratt PJ, Angerhofer A, Lepock JR, Hickey JA, Nick HS, Silverman DN. Probing the active site of human manganese superoxide dismutase: the glutamine 143. Biochemistry. 1998 Apr 7;37(14):4731-9.

    49.  
  49. Guan Y, Hickey MJ, Borgstahl GE, Hallewell RA, Lepock JR, O'Conn Y, Nick HS, Silverman DN, Tainer JA. Crystal structure of Y34F mutant human mitochondrial manganese super dismutase and the functional role of tyrosine 34. Biochemistry. 1998 Apr 7;37(14):4722-30.

    50.  
  50. Crane BR, Arvai AS, Ghosh DK, Wu C, Getzoff ED, Stuehr DJ, Taine Structure of nitric oxide synthase oxygenase dimer with pterin and s Science. 1998 Mar 27;279(5359):2121-6.

    51.  
  51. Marceau M, Forest K, Beretti JL, Tainer J, Nassif X. Consequences of the loss of O-linked glycosylation of meningococcal pilin on piliation and pilus-mediated adhesion. Mol Microbiol. 1998 Feb;27(4):705-15.

    52.  
  52. Koc ON, Gerson SL, Phillips GL, Cooper BW, Kutteh L, Van Zant G, Fox RM, Schupp JE, Tainer N, Lazarus HM. Autologous CD34+ cell transplantation for patients with advanced lym effects of overnight storage on peripheral blood progenitor cell enr engraftment. Bone Marrow Transplant. 1998 Feb;21(4):337-43.

    53.  
  53. Parikh SS, Mol CD, Tainer JA. Base excision repair enzyme family portrait: integrating the structu chemistry of an entire DNA repair pathway. Structure. 1997 Dec 15;5(12):1543-50. Review.

    54.  
  54. Gorman MA, Morera S, Rothwell DG, de La Fortelle E, Mol CD, Tain Hickson ID, Freemont PS. The crystal structure of the human DNA repair endonuclease HAP1 sugg recognition of extra-helical deoxyribose at DNA abasic sites. EMBO J. 1997 Nov 3;16(21):6548-58.

    55.  
  55. Crane BR, Arvai AS, Gachhui R, Wu C, Ghosh DK, Getzoff ED, Stueh JA. The structure of nitric oxide synthase oxygenase domain and inhibito Science. 1997 Oct 17;278(5337):425-31.

    56.  
  56. Fisher CL, Cabelli DE, Hallewell RA, Beroza P, Lo TP, Getzoff ED Computational, pulse-radiolytic, and structural investigations of ly its role in the electrostatic triad of human Cu,Zn superoxide dismut Proteins. 1997 Sep;29(1):103-12.

    57.  
  57. Forest KT, Tainer JA. Type-4 pilus-structure: outside to inside and top to bottom--a minir Gene. 1997 Jun 11;192(1):165-9. Review.

    58.  
  58. Boissinot M, Karnas S, Lepock JR, Cabelli DE, Tainer JA, Getzoff Hallewell RA. Function of the Greek key connection analysed using circular permuta superoxide dismutase. EMBO J. 1997 May 1;16(9):2171-8.

    59.  
  59. Roberts VA, Nachman RJ, Coast GM, Hariharan M, Chung JS, Holman H, Tainer JA. Consensus chemistry and beta-turn conformation of the active core of kinin neuropeptide family. Chem Biol. 1997 Feb;4(2):105-17.

    60.  
  60. Bourne Y, Redford SM, Steinman HM, Lepock JR, Tainer JA, Getzoff Novel dimeric interface and electrostatic recognition in bacterial C superoxide dismutase. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12774-9.

    61.  
  61. Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA. A nucleotide-flipping mechanism from the structure of human uracil-D glycosylase bound to DNA. Nature. 1996 Nov 7;384(6604):87-92.

    62.  
  62. Mol CD, Harris JM, McIntosh EM, Tainer JA. Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and sites formed by three separate subunits. Structure. 1996 Sep 15;4(9):1077-92.

    63.  
  63. Watson MH, Bourne Y, Arvai AS, Hickey MJ, Santiago A, Bernstein JA, Reed SI. A mutation in the human cyclin-dependent kinase interacting protein, interferes with cyclin-dependent kinase binding and biological funct preserves protein structure and assembly. J Mol Biol. 1996 Sep 6;261(5):646-57.

    64.  
  64. Kavli B, Slupphaug G, Mol CD, Arvai AS, Peterson SB, Tainer JA, Excision of cytosine and thymine from DNA by mutants of human uracil glycosylase. EMBO J. 1996 Jul 1;15(13):3442-7.

    65.  
  65. Napolitano EW, Villar HO, Kauvar LM, Higgins DL, Roberts D, Mand SK, Engqvist-Goldstein A, Bukar R, Calio BL, Jack HM, Tainer JA. Glubodies: randomized libraries of glutathione transferase enzymes. Chem Biol. 1996 May;3(5):359-67.

    66.  
  66. Borgstahl GE, Parge HE, Hickey MJ, Johnson MJ, Boissinot M, Hall Lepock JR, Cabelli DE, Tainer JA. Human mitochondrial manganese superoxide dismutase polymorphic varia reduces activity by destabilizing the tetrameric interface. Biochemistry. 1996 Apr 9;35(14):4287-97.

    67.  
  67. Bourne Y, Watson MH, Hickey MJ, Holmes W, Rocque W, Reed SI, Tai Crystal structure and mutational analysis of the human CDK2 kinase c cell cycle-regulatory protein CksHs1. Cell. 1996 Mar 22;84(6):863-74.

    68.  
  68. Ogihara NL, Parge HE, Hart PJ, Weiss MS, Goto JJ, Crane BR, Tsan K, Roe JA, Valentine JS, Eisenberg D, Tainer JA. Unusual trigonal-planar copper configuration revealed in the atomic yeast copper-zinc superoxide dismutase. Biochemistry. 1996 Feb 20;35(7):2316-21.

    69.  
  69. Forest KT, Bernstein SL, Getzoff ED, So M, Tribbick G, Geysen HM Tainer JA. Assembly and antigenicity of the Neisseria gonorrhoeae pilus mapped antibodies. Infect Immun. 1996 Feb;64(2):644-52.

    70.  
  70. Kuhn LA, Swanson CA, Pique ME, Tainer JA, Getzoff ED. Atomic and residue hydrophilicity in the context of folded protein s Proteins. 1995 Dec;23(4):536-47.

    71.  
  71. Parge HE, Forest KT, Hickey MJ, Christensen DA, Getzoff ED, Tain Structure of the fibre-forming protein pilin at 2.6 A resolution. Nature. 1995 Nov 2;378(6552):32-8.

    72.  
  72. Bourne Y, Arvai AS, Bernstein SL, Watson MH, Reed SI, Endicott J Johnson LN, Tainer JA. Crystal structure of the cell cycle-regulatory protein suc1 reveals conformational switch. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10232-6.

    73.  
  73. Phillips JP, Tainer JA, Getzoff ED, Boulianne GL, Kirby K, Hilli Subunit-destabilizing mutations in Drosophila copper/zinc superoxide neuropathology and a model of dimer dysequilibrium. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8574-8.

    74.  
  74. Mol CD, Arvai AS, Sanderson RJ, Slupphaug G, Kavli B, Krokan HE, DW, Tainer JA. Crystal structure of human uracil-DNA glycosylase in complex with a inhibitor: protein mimicry of DNA. Cell. 1995 Sep 8;82(5):701-8.

    75.  
  75. Pond L, Kuhn LA, Teyton L, Schutze MP, Tainer JA, Jackson MR, Pe A role for acidic residues in di-leucine motif-based targeting to th pathway. J Biol Chem. 1995 Aug 25;270(34):19989-97.

    76.  
  76. Thayer MM, Ahern H, Xing D, Cunningham RP, Tainer JA. Novel DNA binding motifs in the DNA repair enzyme endonuclease III c structure. EMBO J. 1995 Aug 15;14(16):4108-20.

    77.  
  77. Barzilay G, Mol CD, Robson CN, Walker LJ, Cunningham RP, Tainer ID. Identification of critical active-site residues in the multifunction repair enzyme HAP1. Nat Struct Biol. 1995 Jul;2(7):561-8.

    78.  
  78. Arvai AS, Bourne Y, Hickey MJ, Tainer JA. Crystal structure of the human cell cycle protein CksHs1: single dom with similarity to kinase N-lobe domain. J Mol Biol. 1995 Jun 23;249(5):835-42.

    79.  
  79. Deng HX, Tainer JA, Mitsumoto H, Ohnishi A, He X, Hung WY, Zhao Hentati A, Siddique T. Two novel SOD1 mutations in patients with familial amyotrophic later sclerosis. Hum Mol Genet. 1995 Jun;4(6):1113-6. No abstract available.

    80.  
  80. Sjalander A, Beckman G, Deng HX, Iqbal Z, Tainer JA, Siddique T. The D90A mutation results in a polymorphism of Cu,Zn superoxide dism is prevalent in northern Sweden and Finland. Hum Mol Genet. 1995 Jun;4(6):1105-8. No abstract available.

    81.  
  81. McTigue MA, Bernstein SL, Williams DR, Tainer JA. Purification and crystallization of a schistosomal glutathione S-tra Proteins. 1995 May;22(1):55-7.

    82.  
  82. Mol CD, Arvai AS, Slupphaug G, Kavli B, Alseth I, Krokan HE, Tai Crystal structure and mutational analysis of human uracil-DNA glycos structural basis for specificity and catalysis. Cell. 1995 Mar 24;80(6):869-78.

    83.  
  83. Mol CD, Kuo CF, Thayer MM, Cunningham RP, Tainer JA. Structure and function of the multifunctional DNA-repair enzyme exon Nature. 1995 Mar 23;374(6520):381-6.

    84.  
  84. McTigue MA, Williams DR, Tainer JA. Crystal structures of a schistosomal drug and vaccine target: glutat S-transferase from Schistosoma japonica and its complex with the lea antischistosomal drug praziquantel. J Mol Biol. 1995 Feb 10;246(1):21-7.

    85.  
  85. Tainer JA, Thayer MM, Cunningham RP. DNA repair proteins. Curr Opin Struct Biol. 1995 Feb;5(1):20-6. Review.

    86.  
  86. Arvai AS, Bourne Y, Williams D, Reed SI, Tainer JA. Crystallization and preliminary crystallographic study of human CksH cycle regulatory protein. Proteins. 1995 Jan;21(1):70-3.

    87.  

Recent TSRI Graduates from the Tainer Lab

Former members of the Tainer Lab