Deriving Function From Structure

Approaches and Limitations
  • Annabel E. Todd
Part of the Springer Protocols Handbooks book series (SPH)


The fold and biochemical activity of a protein are tightly coupled. Once a protein is characterized, it is usual to determine its structure in order to derive an atomic descrip- tion of its molecular mechanism. The fold reveals interaction surfaces, ligand-binding pockets, and the precise juxtaposition of functional groups.


Protein Data Bank Functional Site Protein Data Bank File Functional Residue Triacylglycerol Lipase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Burley, S. K., Almo, S. C., Bonanno, J. B. et al. (1999) Structural genomics: beyond the human genome project. Nature Genet. 23, 151–157.PubMedCrossRefGoogle Scholar
  2. 2.
    Brenner, S. E. (2001) A tour of structural genomics. Nature Rev. Genet. 2, 801–809.PubMedCrossRefGoogle Scholar
  3. 3.
    Shapiro, L. and Harris, T. (2000) Finding function through structural genomics. Curr. Opin. Biotech. 11, 31–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Chothia, C. and Lesk, A. (1986) The relation between the divergence of sequence and structure in proteins. EMBO J. 5, 823–826.PubMedGoogle Scholar
  5. 5.
    Ollis, D. L., Cheah, E., Cygler, M., et al. (1992) The ga/gb hydrolase fold. Protein Eng. 5, 197–211.PubMedCrossRefGoogle Scholar
  6. 6.
    Hegyi, H. and Gerstein, M. (1999) The relationship between protein structure and function: a comprehensive survey with application to the yeast genome. J. Mol. Biol. 288, 147–164.PubMedCrossRefGoogle Scholar
  7. 7.
    Teichmann, S. A., Park, J., and Chothia, C. (1998) Structural assignments to the proteins of Mycoplasma genitalium show that they have been formed by extensive gene duplica-tions and domain rearrangements. Proc. Natl. Acad. Sci. USA 95, 14,658–14,663.PubMedCrossRefGoogle Scholar
  8. 8.
    Teichmann, S. A., Chothia, C., and Gerstein, M. (1999) Advances in structural genomics. Curr. Opin. Struct. Biol. 9, 390–399.PubMedCrossRefGoogle Scholar
  9. 9.
    Berman, H. M., Westbrook, J., Feng, Z., et al. (2000) The Protein Data Bank. Nucl. Acids Res. 28, 235–242.PubMedCrossRefGoogle Scholar
  10. 10.
    International Human Genome Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921.CrossRefGoogle Scholar
  11. 11.
    Wistow, G. J., Mulders, J. W. M., and Dejong, W. (1987) The enzyme lactate dehydrogenase as a structural protein in avian and crocodilian lenses. Nature 326, 622–624.PubMedCrossRefGoogle Scholar
  12. 12.
    Jeffery, C. (1999) Moonlighting proteins. Trends Biochem. Sci. 24, 8–11.PubMedCrossRefGoogle Scholar
  13. 13.
    Mondrek, B. and Lee, C. (2002) A genomic view of alternative splicing. Nat. Genet. 30, 13–19.CrossRefGoogle Scholar
  14. 14.
    Kriventseva, E. V., Koch, I., Apweiler, R., et al. (2003) Increase of functional diversity by alternative splicing. Trends Genet. 19, 124–128.PubMedCrossRefGoogle Scholar
  15. 15.
    Wright, P. E. and Dyson, J. (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J. Mol. Biol. 293, 321–331.PubMedCrossRefGoogle Scholar
  16. 16.
    Liu, J., Tan, H., and Rost, B. (2002) Loopy proteins appear conserved in evolution. J. Mol. Biol. 322, 53–64.PubMedCrossRefGoogle Scholar
  17. 17.
    Postingl, H., Henrick, K., and Thornton, J. M. (2000) Discriminating between homodimeric and monomeric proteins in the crystalline state. Proteins: Struct. Func. Genet. 41,47–57.CrossRefGoogle Scholar
  18. 18.
    Zarembinski, T. I., Hung, L.-W., Mueller-Dieckmann, H.-J., et al. (1998) Structure-based assignment of the biochemical function of a hypothetical protein: a test case for structural genomics. Proc. Natl. Acad. Sci. USA, 95, 15189–15193.PubMedCrossRefGoogle Scholar
  19. 19.
    Martin, A. C. R., Orengo, C. A., Hutchinson, E. G., et al. (1998) Protein folds and functions. Structure 6, 875–884.PubMedCrossRefGoogle Scholar
  20. 20.
    Anantharaman, V., Aravind, L., and Koonin, E. V. (2003) Emergence of diverse biochemical activities in evolutionary conserved structural scaffolds of proteins. Curr. Opin. Chem. Biol. 7, 12–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Thornton, J. M., Todd, A. E., Milburn, D., Borkakoti, N., and Orengo, C. A. (2000) From structure to function: approaches and limitations. Nat. Struct. Biol. 7, 991–994.PubMedCrossRefGoogle Scholar
  22. 22.
    Moult, J. and Melamud, E. (2000) From fold to function. Curr. Opin. Struct. Biol. 10, 384–389.PubMedCrossRefGoogle Scholar
  23. 23.
    Orengo, A., Michie, A. D., Jones, S., Jones, D. T., Swindells, M. B. and Thornton, J. M. (1997) CATH-a hierarchic classification of protein domain structures. Structure 5, 1093–1108.PubMedCrossRefGoogle Scholar
  24. 24.
    Murzin, A. G., Brenner, S. E., Hubbard, T., and Chothia, C. (1995) SCOP-A structural classification of proteins database for the investigation of sequences and structures. J. Mol. Biol., 247, 536–540.PubMedGoogle Scholar
  25. 25.
    Wilson, C. A., Kreychman, J., and Gerstein, M. (2000) Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores. J. Mol. Biol. 297, 233–249.PubMedCrossRefGoogle Scholar
  26. 26.
    Devos, D. and Valencia, A. (2000) Practical limits of function prediction. Proteins: Struct. Func. Genet. 41, 98–107.CrossRefGoogle Scholar
  27. 27.
    Todd, A. E., Orengo, C. A., and Thornton, J. M. (2001) Evolution of function in protein superfamilies, from a structural perspective. J. Mol. Biol. 307, 1113–1143.PubMedCrossRefGoogle Scholar
  28. 28.
    Rost, B. (2002) Function less conserved than anticipated. J. Mol. Biol. 318, 595–608.PubMedCrossRefGoogle Scholar
  29. 29.
    Grishin, N. V. (2001) Fold change in evolution of protein structures. J. Struct. Biol. 134, 167–185.PubMedCrossRefGoogle Scholar
  30. 30.
    Chothia, C. (1992) One thousand families for the molecular biologist. Nature 357,543–544.PubMedCrossRefGoogle Scholar
  31. 31.
    Orengo, C. A., Jones, D. T., and Thornton, J. M. (1994) Protein superfamilies and domain superfolds. Nature 372, 631–634.PubMedCrossRefGoogle Scholar
  32. 32.
    Nagano, N., Orengo, C. A., and Thornton, J. M. (2002) One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions. J. Mol. Biol. 321, 741–765.PubMedCrossRefGoogle Scholar
  33. 33.
    Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) (1992) Enzyme Nomenclature, Academic Press, New York, NY.Google Scholar
  34. 34.
    Russell, R. B. Sasieni, P. D., and Sternberg, M. J. E. (1998) Supersites within superfolds. Binding site similarity in the absence of homology. J. Mol. Biol. 282, 903–918.PubMedCrossRefGoogle Scholar
  35. 35.
    Wallace, A. C., Laskowski, R. A., and Thornton, J. M. (1996) Derivation of 3D coordinate templates for searching structural databases: application to the Ser-His-Asp catalytic triads of the serine proteinases and lipases. Protein Sci. 5, 1001–1013.PubMedCrossRefGoogle Scholar
  36. 36.
    Bartlett, G. J., Porter, C. T., Borkakorti, N., and Thornton, J. M. (2002) Analysis of catalytic residues in enzyme active sites. J. Mol. Biol. 324, 105–121.PubMedCrossRefGoogle Scholar
  37. 37.
    Orengo, C. A., Todd, A. E., and Thornton, J. M. (1999) From protein structure to function. Curr. Opin. Struct. Biol. 9, 374–382.PubMedCrossRefGoogle Scholar
  38. 38.
    Lichtarge, O. and Sowa, M. E. (2002) Evolutionary predictions of binding surfaces and interactions. Curr. Opin. Struct. Biol. 12, 21–27.PubMedCrossRefGoogle Scholar
  39. 39.
    Sotriffer, C. and Klebe, G. (2002) Identification and mapping of small-molecule binding sites in proteins: computational tools for structure-based drug design. Il Farmaco 57, 243–251.PubMedCrossRefGoogle Scholar
  40. 40.
    Campbell, S. J., Gold, N. D., Jackson, R. M., and Westhead, D. R. (2003) Ligand binding: functional site location, similarity and docking. Curr. Opin. Struct. Biol. 13, 389–395.PubMedCrossRefGoogle Scholar
  41. 41.
    Kinoshita, K. and Nakamura, H. (2003) Protein informatics towards function identification. Curr. Opin. Struct. Biol. 13, 396–400.PubMedCrossRefGoogle Scholar
  42. 42.
    Artymiuk, P. J., Poirrette, A. R., Grindley, H. M., Rice, D. W., and Willett, P. (1994) A graph-theoretic approach to the identification of 3-dimensional patterns of amino-acid side-chains in protein structures. J. Mol. Biol. 243, 327–344.PubMedCrossRefGoogle Scholar
  43. 43.
    Spriggs, R. V., Artymiuk, P. J., and Willett, P. (2003) Searching for patterns of amino acids in 3D protein structures. J. Chem. Inf. Sci. 43, 412–421.Google Scholar
  44. 44.
    Wallace, A. C., Borkakorti, N., and Thornton, J. M. (1997) TESS: a geometric hashing algorithm for deriving 3D coordinate templates for searching structural databases: appli-cation to enzyme active-sites. Protein Sci. 6, 2308–2323.PubMedCrossRefGoogle Scholar
  45. 45.
    Fetrow, J. S. and Skolnick, J. (1998) Method for prediction of protein function from sequence using the sequence-to-structure-to-function paradigm with application to glutaredoxins/thioredoxins and T1 ribonucleases. J. Mol. Biol. 281, 949–968.PubMedCrossRefGoogle Scholar
  46. 46.
    Russell, R. B. (1998) Identification of protein three-dimensional side-chain patterns: new examples of convergent evolution. J. Mol. Biol. 279, 1211–1227.PubMedCrossRefGoogle Scholar
  47. 47.
    Kleywegt, G. (1999) Recognition of spatial motifs in protein structures. J. Mol. Biol. 285, 1887–1897.PubMedCrossRefGoogle Scholar
  48. 48.
    Jonassen, I., Eidhammer, I., and Taylor, W. R. (1999) Discovery of local packing motifs in protein structures. Proteins 34, 206–219.PubMedCrossRefGoogle Scholar
  49. 49.
    Oldfield, T. J. (2002) Data mining the protein data bank: residue interactions. Proteins: Struct. Func. Genet. 49, 510–528.CrossRefGoogle Scholar
  50. 50.
    Wangikar, P. P., Tendulkar, A. V., Ramya, S., Mali, D. N., and Sarawagi, S. (2003) Functional sites in protein families uncovered via an objective and automated graph theoretic approach. J. Mol. Biol. 326, 955–978.PubMedCrossRefGoogle Scholar
  51. 51.
    Hamelryck, T. (2003) Efficient identification of side-chain patterns using a multidimensional index tree. Proteins: Struct. Func. Genet. 51, 96–108.CrossRefGoogle Scholar
  52. 52.
    Zhao, S., Morris, G. M., Olson, A. J., and Goodsell, D. S. (2001) Recognition templates for predicting adenylate-binding sites in proteins. J. Mol. Biol. 314, 1245–1255.PubMedCrossRefGoogle Scholar
  53. 53.
    Schmitt, S., Kuhn, D., and Klebe, G. (2002) A new method to detect related function among proteins independent of sequence and fold homology. J. Mol. Biol. 323, 387–406.PubMedCrossRefGoogle Scholar
  54. 54.
    Kinoshita, K., Furui, J., and Nakamura, H. (2001) Identification of protein functions from a molecular surface database, eF-site. J. Struct. Func. Genomics 2, 9–22.CrossRefGoogle Scholar
  55. 55.
    Casari, G., Sander, C., and Valencia, A. (1995) A method to predict functional residues in proteins. Nat. Struct. Biol. 2, 171–178.PubMedCrossRefGoogle Scholar
  56. 56.
    Lichtarge, O., Bourne, H. R., and Cohen, F. E. (1996) An evolutionary trace method defines binding surfaces common to protein families. J. Mol. Biol. 257, 342–358.PubMedCrossRefGoogle Scholar
  57. 57.
    Aloy, P., Querol, E., Aviles, F. X., and Sternberg, M. J. E. (2001) Automated structurebased prediction of functional sites in proteins: applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking. J. Mol. Biol. 311, 395–408.PubMedCrossRefGoogle Scholar
  58. 58.
    Landgraf, R., Xenarios, I., and Eisenberg, D. (2001) Three-dimensional clustering analysis identifies interfaces and functional residue clusters in proteins. J. Mol. Biol. 307, 1487–1502.PubMedCrossRefGoogle Scholar
  59. 59.
    Armon, A., Graur, D., and Ben-Tal, N. (2001) ConSurf: an algorithmic tool for the identification of functional regions in proteins by surface mapping of phylogenetic informa-tion. J. Mol. Biol. 307, 447–463.PubMedCrossRefGoogle Scholar
  60. 60.
    Pupko, T., Bell, R. E., Mayrose, I., Glaser, F., and Ben-Tal, N. (2002) Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues. Bioinformatics 18 Suppl., S71–S77.PubMedGoogle Scholar
  61. 61.
    Elcock, A. H. (2001) Prediction of functionally important residues based solely on the computed energetics of protein structure. J. Mol. Biol. 312, 885–896.PubMedCrossRefGoogle Scholar
  62. 62.
    Ondrechen, M. J., Clifton, J. G., and Ringe, D. (2001) THEMATICS: a simple computational predictor of enzyme function from structure. Proc. Natl. Acad. Sci. USA 98, 12,473–12,478.PubMedCrossRefGoogle Scholar
  63. 63.
    Laskowski, R. A. (1995) SURFNET: a program for visualising molecular surfaces, cavities and intermolecular interactions. J. Mol. Graph. 13, 323–330.PubMedCrossRefGoogle Scholar
  64. 64.
    Peters, K. P., Fauck, J., and Frommel, C. (1996) The automatic search for ligand binding sites in proteins of known three-dimensional structure using only geometric criteria. J. Mol. Biol. 256, 201–213.PubMedCrossRefGoogle Scholar
  65. 65.
    Hendlich, M., Rippmann, F., and Barnickel, G. (1997) LIGSITE: automatic and efficient detection of potential small-molecule binding sites in proteins. J. Mol. Graph. Model. 15, 359–363.PubMedCrossRefGoogle Scholar
  66. 66.
    Brady Jr, G. P. and Stouten, P. F. W. (2000) Fast prediction and visualization of protein binding pockets with PASS. J. Comput. Aided Mol. Des. 14, 383–401.PubMedCrossRefGoogle Scholar
  67. 67.
    Ota, M., Kinoshita, K., and Nishikawa, K. (2003) Prediction of catalytic residues in enzymes based on known tertiary structure, stability profile, and sequence conservation. J. Mol. Biol. 327, 1053–1064.PubMedCrossRefGoogle Scholar
  68. 68.
    Gutteridge, A., Bartlett, G. J., and Thornton, J. M. (2003) Using a neural network and spatial clustering to predict the location of active sites in enzymes. J. Mol. Biol. 330, 719–734.PubMedCrossRefGoogle Scholar
  69. 69.
    Dobson, P. D. and Doig, A. J. (2003) Distinguishing enzyme structures from non-enzymes without alignments. J. Mol. Biol. 330, 771–783.PubMedCrossRefGoogle Scholar
  70. 70.
    Laskowski, R. A., Luscombe, N. M., Swindells, M. B., and Thornton, J. M. (1996) Protein clefts in molecular recognition and function. Protein Sci. 5, 2438–2452.PubMedGoogle Scholar
  71. 71.
    Warshel, A. (1978) Energetics of enzyme catalysis. Proc. Natl. Acad. Sci. USA 75, 5250–5254.PubMedCrossRefGoogle Scholar
  72. 72.
    Beadle, B. M. and Schoichet, B. K. (2002) Structural bases of stability-function tradeoffs in enzymes. J. Mol. Biol. 321, 285–296.PubMedCrossRefGoogle Scholar
  73. 73.
    Jones, S. and Thornton, J. M. (1997) Analysis of protein-protein interaction sites using surface patches. J. Mol. Biol. 272, 121–132.PubMedCrossRefGoogle Scholar
  74. 74.
    Lo Conte, L., Chothia, C., and Janin, J. (1999) The atomic structure of protein-protein recognition sites. J. Mol. Biol. 285, 2177–2198.PubMedCrossRefGoogle Scholar
  75. 75.
    Nooren, I. M. A. and Thornton, J. M. (2003) Structural characterization and functional significance of transient protein-protein interactions. J. Mol. Biol. 325, 991–1018.PubMedCrossRefGoogle Scholar
  76. 76.
    Nooren, I. M. A. and Thornton, J. M. (2003) Diversity of protein-protein interactions. EMBO J. 22, 3486–3492.PubMedCrossRefGoogle Scholar
  77. 77.
    Ofran, Y. and Rost, B. (2003) Analysing six types of protein-protein interfaces. J. Mol. Biol. 325, 377–387.PubMedCrossRefGoogle Scholar
  78. 78.
    Jones, S. and Thornton, J. M. (1997) Prediction of protein-protein interaction sites using patch analysis. J. Mol. Biol. 272, 133–143.PubMedCrossRefGoogle Scholar
  79. 79.
    Stark, A., Sunyaev, S., and Russell, R. B. (2003) A model for statistical significance of local similarities in structure. J. Mol. Biol. 326, 1307–1316.PubMedCrossRefGoogle Scholar
  80. 80.
    Barker, J. A. and Thornton, J. M. (2003) An algorithm for constraint-based structural template matching: application to 3D templates with statistical analysis. Bioinformatics 19, 1644–1649.PubMedCrossRefGoogle Scholar
  81. 81.
    Madabushi, S., Yao, H., Marsh, M., et al. (2002) Structural clusters of evolutionary trace residues are statistically significant and common in proteins. J. Mol. Biol. 316, 139–154.PubMedCrossRefGoogle Scholar
  82. 82.
    Sowa, M. E., He, W., Wensel, T. G., and Lichtarge, O. (2000) A regulator of G protein signaling interaction surface linked to effector specificity. Proc. Natl. Acad. Sci. USA 97, 1483–1488.PubMedCrossRefGoogle Scholar
  83. 83.
    Sowa, M. E., He, W., Slep, K. C., Kercher, M. A., Lichtarge, O., and Wensel, T. G. (2001) Prediction and confirmation of a site critical for effector regulation of RGS domain activ-ity. Nat. Struct. Biol. 8, 234–237.PubMedCrossRefGoogle Scholar
  84. 84.
    Slep, K. C., Kercher, M. A., He, W., Cowan, C. W., Wensel, T. G., and Sigler, P. B. (2001) Structural determinants for regulation of phosphodiesterase by a G protein at 2.0Å. Nature 409, 1071–1077.PubMedCrossRefGoogle Scholar
  85. 85.
    Porter, C. T., Bartlett, G. J., and Thornton, J. M. (2004) The Catalytic Site Atlas (CSA): a resource of catalytic sites and residues identified in enzymes using structural data. Nucl. Acids Res. 32, D129–D133.PubMedCrossRefGoogle Scholar
  86. 86.
    Fetrow, J. S., Siew, N., Di Gennaro, J. A., Martinez-Yamount, M., Dyson, H. J., and Skolnick, J. (2001) Genomic-scale comparison of sequence-and structure-based meth-ods of function prediction: does structure provide additional insight? Protein Sci. 10, 1005–1014.PubMedCrossRefGoogle Scholar
  87. 87.
    Stark, A. and Russell, R. B. (2003) Annotation in three dimensions. PINTS: patterns in non-homologous tertiary structures. Nucl. Acids Res. 31, 3341–3344.PubMedCrossRefGoogle Scholar
  88. 88.
    Yao, H., Kristensen, D. M., Mihalek, I., et al. (2003) An accurate, sensitive, and scalable method to identify functional sites in protein structures. J. Mol. Biol. 326, 255–261.PubMedCrossRefGoogle Scholar
  89. 89.
    Boeckmann, B., Bairoch, A., Apweiler, R., et al. (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucl. Acids Res. 31, 365–370.PubMedCrossRefGoogle Scholar
  90. 90.
    Todd, A. E. (2001) Evolution of function in protein superfamilies. PhD thesis, University College London.Google Scholar
  91. 91.
    Jensen, R. A. (1976) Enzyme recruitment in evolution of new function. Annu. Rev. Microbiol. 30, 409–425.PubMedCrossRefGoogle Scholar
  92. 92.
    O’Brien, P. J. and Herschlag, D. (1999) Catalytic promiscuity and the evolution of new enzymatic activities. Chem. Biol. 6, r91–r105.CrossRefGoogle Scholar
  93. 93.
    Petsko, G. A., Kenyon, G. L., Gerlt, J. A., Ringe, D., and Kozarich, J. W. (1993) On the origin of enzymatic species. Trends Biochem. Sci. 18, 372–376.PubMedCrossRefGoogle Scholar
  94. 94.
    Babbitt, P. and Gerlt, J. A. (1997) Understanding enzyme superfamilies-chemistry as the fundamental determinant in the evolution of new catalytic activities. J. Biol. Chem. 272, 30,591–30,594.PubMedCrossRefGoogle Scholar
  95. 95.
    Gerlt, J. A. and Babbitt, P. C. (1998) Mechanistically diverse enzyme superfamilies: the importance of chemistry in the evolution of catalysis. Curr. Opin. Chem. Biol. 2, 607–612.PubMedCrossRefGoogle Scholar
  96. 96.
    Babbitt, P. C., Hasson, M. S., Wedekind, J. E., et al. (1996) The enolase superfamily: a general strategy for enzyme-catalysed abstraction of the ?-protons of carboxylic acids. Biochemistry 35, 16,489–16,501.PubMedCrossRefGoogle Scholar
  97. 97.
    Todd, A. E., Orengo, C. A., and Thornton, J. M. (2002) Plasticity of enzyme active sites. Trends Biochem. Sci. 27, 419–426.PubMedCrossRefGoogle Scholar
  98. 98.
    Wilce, M. C. J., Board, P. G., Feil, S. C., and Parker, M. W. (1995) Crystal structure of a theta-class glutathione transferase. EMBO J. 14, 2133–2143.PubMedGoogle Scholar
  99. 99.
    Ilari, A., Stefanini, S., Chiancone, E., and Tsernoglou, D. (2000) The dodecameric ferritin from L. innocua contains a novel intersubunit iron-binding site. Nat. Struct. Biol. 7, 38–43.PubMedCrossRefGoogle Scholar
  100. 100.
    Holm, L. and Sander, C. (1997) New structure-novel fold? Structure 5, 165–171.PubMedCrossRefGoogle Scholar
  101. 101.
    Zhang, C. and Kim, S.-H. (2003) Overview of structural genomics: from structure to func-tion. Curr. Opin. Chem. Biol. 7, 28–32.PubMedCrossRefGoogle Scholar
  102. 102.
    Sanishvili, R., Yakunin, A. F., Laskowski, R. A., et al. (2003) Integrating structure, bioinformatics and enzymology to discover function. J. Biol. Chem. 278, 26,039–26,045.PubMedCrossRefGoogle Scholar
  103. 103.
    Volz, K. (1999) A test case for structure-based functional assignment: the 1.2 Å crystal structure of the yjgF gene product from Escherichia coli. Protein Sci. 8, 2428–2437.Google Scholar
  104. 104.
    Hwang, K. Y., Chung, J. H., Kim, S.-H., Han, Y. S., and Cho, Y. (1999) Structure-based identification of a novel NTPase from Methanococcus jannaschii. Nat. Struct. Biol. 6, 691–696.CrossRefGoogle Scholar
  105. 105.
    Cort, J. R., Yee, A., Edwards, A. M., Arrowsmith, C. H., and Kennedy, M. A. (2000) Structure-based functional classification of hypothetical protein MTH538 from Methano-bacterium thermoautotrophicum. J. Mol. Biol. 302, 189–203.Google Scholar
  106. 106.
    Teplova, M., Tereshko, V., Sanishvili, R., et al. (2000) The structure of the yrdC gene product from Escherichia coli reveals a new fold and suggests a role in RNA binding. Protein Sci. 9, 2557–2566.PubMedCrossRefGoogle Scholar
  107. 107.
    Marcotte, E. M. (2000) Computational genetics: finding protein function by non-homol-ogy methods. Curr. Opin. Struct. Biol. 10, 359–365.PubMedCrossRefGoogle Scholar
  108. 108.
    Artymiuk, P. J., Poirrette, A. R., Rice, D. W., and Willett, P. (1997) A polymerase I palm in adenylyl cyclase? Nature 388, 33–34.PubMedCrossRefGoogle Scholar
  109. 109.
    Bryant, S. H., Janin, J., Liu, Y., Ruoho, A. E., Zhang, G., and Hurley, J. H. (1997) A polymerase I palm in adenylyl cyclase?-reply. Nature 388, 34.CrossRefGoogle Scholar
  110. 110.
    Tesmer, J. J. T., Sunahara, R. K., Gilman, A. G., and Sprang, S. R. (1997) Crystal struc-ture of the catalytic domains of adenylyl cyclase in a complex with Gsga.GTP#x03B3;S. Science 278, 1907–1916.PubMedCrossRefGoogle Scholar
  111. 111.
    Taylor, W. R. and Orengo, C. A. (1989) Protein structure alignment. J. Mol. Biol. 208, 1–22.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, nJ 2005

Authors and Affiliations

  • Annabel E. Todd
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity College LondonLondon

Personalised recommendations