Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1996 Jun;5(6):1001–1013. doi: 10.1002/pro.5560050603

Derivation of 3D coordinate templates for searching structural databases: application to Ser-His-Asp catalytic triads in the serine proteinases and lipases.

A C Wallace 1, R A Laskowski 1, J M Thornton 1
PMCID: PMC2143436  PMID: 8762132

Abstract

It is well established that sequence templates (e.g., PROSITE) and databases are powerful tools for identifying biological function and tertiary structure for an unknown protein sequence. Here we describe a method for automatically deriving 3D templates from the protein structures deposited in the Brookhaven Protein Data Bank. As an example, we describe a template derived for the Ser-His-Asp catalytic triad found in the serine proteases and triacylglycerol lipases. We find that the resultant template provides a highly selective tool for automatically differentiating between catalytic and noncatalytic Ser-His-Asp associations. When applied to nonproteolytic proteins, the template picks out two "non-esterase" catalytic triads that may be of biological relevance. This suggests that the development of databases of 3D templates, such as those that currently exist for protein sequence templates, will help identify the functions of new protein structures as they are determined and pinpoint their functionally important regions.

Full Text

The Full Text of this article is available as a PDF (15.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Artymiuk P. J., Poirrette A. R., Grindley H. M., Rice D. W., Willett P. A graph-theoretic approach to the identification of three-dimensional patterns of amino acid side-chains in protein structures. J Mol Biol. 1994 Oct 21;243(2):327–344. doi: 10.1006/jmbi.1994.1657. [DOI] [PubMed] [Google Scholar]
  2. Attwood T. K., Beck M. E., Bleasby A. J., Parry-Smith D. J. PRINTS--a database of protein motif fingerprints. Nucleic Acids Res. 1994 Sep;22(17):3590–3596. [PMC free article] [PubMed] [Google Scholar]
  3. Bairoch A., Boeckmann B. The SWISS-PROT protein sequence data bank: current status. Nucleic Acids Res. 1994 Sep;22(17):3578–3580. [PMC free article] [PubMed] [Google Scholar]
  4. Bairoch A., Boeckmann B. The SWISS-PROT protein sequence data bank: current status. Nucleic Acids Res. 1994 Sep;22(17):3578–3580. [PMC free article] [PubMed] [Google Scholar]
  5. Bairoch A., Bucher P. PROSITE: recent developments. Nucleic Acids Res. 1994 Sep;22(17):3583–3589. [PMC free article] [PubMed] [Google Scholar]
  6. Barth A., Frost K., Wahab M., Brandt W., Schadler H. D., Franke R. Classification of serine proteases derived from steric comparisons of their active sites, part II: "Ser, His, Asp arrangements in proteolytic and nonproteolytic proteins". Drug Des Discov. 1994 Nov;12(2):89–111. [PubMed] [Google Scholar]
  7. Barth A., Wahab M., Brandt W., Frost K. Classification of serine proteases derived from steric comparisons of their active sites. Drug Des Discov. 1993;10(4):297–317. [PubMed] [Google Scholar]
  8. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  9. Blow D. M., Birktoft J. J., Hartley B. S. Role of a buried acid group in the mechanism of action of chymotrypsin. Nature. 1969 Jan 25;221(5178):337–340. doi: 10.1038/221337a0. [DOI] [PubMed] [Google Scholar]
  10. Brady L., Brzozowski A. M., Derewenda Z. S., Dodson E., Dodson G., Tolley S., Turkenburg J. P., Christiansen L., Huge-Jensen B., Norskov L. A serine protease triad forms the catalytic centre of a triacylglycerol lipase. Nature. 1990 Feb 22;343(6260):767–770. doi: 10.1038/343767a0. [DOI] [PubMed] [Google Scholar]
  11. Brzozowski A. M., Derewenda U., Derewenda Z. S., Dodson G. G., Lawson D. M., Turkenburg J. P., Bjorkling F., Huge-Jensen B., Patkar S. A., Thim L. A model for interfacial activation in lipases from the structure of a fungal lipase-inhibitor complex. Nature. 1991 Jun 6;351(6326):491–494. doi: 10.1038/351491a0. [DOI] [PubMed] [Google Scholar]
  12. Derewenda U., Brzozowski A. M., Lawson D. M., Derewenda Z. S. Catalysis at the interface: the anatomy of a conformational change in a triglyceride lipase. Biochemistry. 1992 Feb 11;31(5):1532–1541. doi: 10.1021/bi00120a034. [DOI] [PubMed] [Google Scholar]
  13. Fischer D., Wolfson H., Lin S. L., Nussinov R. Three-dimensional, sequence order-independent structural comparison of a serine protease against the crystallographic database reveals active site similarities: potential implications to evolution and to protein folding. Protein Sci. 1994 May;3(5):769–778. doi: 10.1002/pro.5560030506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Glusker J. P. Structural aspects of metal liganding to functional groups in proteins. Adv Protein Chem. 1991;42:1–76. doi: 10.1016/s0065-3233(08)60534-3. [DOI] [PubMed] [Google Scholar]
  15. Hayashi R., Moore S., Stein W. H. Serine at the active center of yeast carboxypeptidase. J Biol Chem. 1973 Dec 25;248(24):8366–8369. [PubMed] [Google Scholar]
  16. Ke H. Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63 A resolution. J Mol Biol. 1992 Nov 20;228(2):539–550. doi: 10.1016/0022-2836(92)90841-7. [DOI] [PubMed] [Google Scholar]
  17. Liao D. I., Breddam K., Sweet R. M., Bullock T., Remington S. J. Refined atomic model of wheat serine carboxypeptidase II at 2.2-A resolution. Biochemistry. 1992 Oct 13;31(40):9796–9812. doi: 10.1021/bi00155a037. [DOI] [PubMed] [Google Scholar]
  18. Marquart M., Deisenhofer J., Huber R., Palm W. Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 A and 1.0 A resolution. J Mol Biol. 1980 Aug 25;141(4):369–391. doi: 10.1016/0022-2836(80)90252-1. [DOI] [PubMed] [Google Scholar]
  19. McGrath M. E., Vásquez J. R., Craik C. S., Yang A. S., Honig B., Fletterick R. J. Perturbing the polar environment of Asp102 in trypsin: consequences of replacing conserved Ser214. Biochemistry. 1992 Mar 31;31(12):3059–3064. doi: 10.1021/bi00127a005. [DOI] [PubMed] [Google Scholar]
  20. Merritt E. A., Murphy M. E. Raster3D Version 2.0. A program for photorealistic molecular graphics. Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):869–873. doi: 10.1107/S0907444994006396. [DOI] [PubMed] [Google Scholar]
  21. Murzin A. G., Brenner S. E., Hubbard T., Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995 Apr 7;247(4):536–540. doi: 10.1006/jmbi.1995.0159. [DOI] [PubMed] [Google Scholar]
  22. Noble M. E., Cleasby A., Johnson L. N., Egmond M. R., Frenken L. G. The crystal structure of triacylglycerol lipase from Pseudomonas glumae reveals a partially redundant catalytic aspartate. FEBS Lett. 1993 Sep 27;331(1-2):123–128. doi: 10.1016/0014-5793(93)80310-q. [DOI] [PubMed] [Google Scholar]
  23. Ollis D. L., Cheah E., Cygler M., Dijkstra B., Frolow F., Franken S. M., Harel M., Remington S. J., Silman I., Schrag J. The alpha/beta hydrolase fold. Protein Eng. 1992 Apr;5(3):197–211. doi: 10.1093/protein/5.3.197. [DOI] [PubMed] [Google Scholar]
  24. Orengo C. A., Flores T. P., Taylor W. R., Thornton J. M. Identification and classification of protein fold families. Protein Eng. 1993 Jul;6(5):485–500. doi: 10.1093/protein/6.5.485. [DOI] [PubMed] [Google Scholar]
  25. Perona J. J., Craik C. S. Structural basis of substrate specificity in the serine proteases. Protein Sci. 1995 Mar;4(3):337–360. doi: 10.1002/pro.5560040301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sussman J. L., Harel M., Frolow F., Oefner C., Goldman A., Toker L., Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science. 1991 Aug 23;253(5022):872–879. doi: 10.1126/science.1678899. [DOI] [PubMed] [Google Scholar]
  27. Takeuchi Y., Satow Y., Nakamura K. T., Mitsui Y. Refined crystal structure of the complex of subtilisin BPN' and Streptomyces subtilisin inhibitor at 1.8 A resolution. J Mol Biol. 1991 Sep 5;221(1):309–325. [PubMed] [Google Scholar]
  28. Taylor W. R. Pattern matching methods in protein sequence comparison and structure prediction. Protein Eng. 1988 Jul;2(2):77–86. doi: 10.1093/protein/2.2.77. [DOI] [PubMed] [Google Scholar]
  29. Wright C. S., Alden R. A., Kraut J. Structure of subtilisin BPN' at 2.5 angström resolution. Nature. 1969 Jan 18;221(5177):235–242. doi: 10.1038/221235a0. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES