[ General description ] [ Acknowledgements ] [ Links ] [ References ]

Hierarchical Classification of Hydrolases Catalytic Sites

General Information
Data access	You can access the database by one of the following methods: Explore the hierarchy of classes Search for a specific protein
Statistics	The current release 1.2 (May 2005) of the database contains 1162 classified hydrolases 87 classes References to 6302 PDB structures 68 manually drawn schemes of catalytic mechanisms 56 3D-viewable images of catalytic sites 594 literature references
Data model	Main objects of the database are proteins and classes. Each class unites hydrolases with the same type of the catalytic site. Classes are organized into a hierarchy. Hydrolases can be linked to any class, not necessarily to a terminal one. The relation between a class and its subclass in the hierarchy is that catalytic site of the subclass refines catalytic site of the base class, i.e. the former contains all catalytic residues of the base class site and some additional residues. For example, esterase from Streptomyces scabiei with unusual catalytic dyad Ser-His belongs to class S.01 (Serine hydrolases with Ser-His dyad) and more abundant hydrolases like trypsin or subtilisin belong to subclass S.01.01 (Hydrolases with Ser-His-Asp/Glu triad) of that class.
Hierarchy organisation	To build the hierarchy, catalytic residues are ordered so that more important ones are considered first. Three simple rules are applied: The residue forming a covalent bond with substrate during reaction takes priority. The further a residue from a reactive center, the lower its priority. If a catalytic site includes metal ion(s), then it is classified according to nature and the number of the ions. If two catalytic sites are equal in composition but known to have different catalytic mechanisms, then they are placed in different classes. Therefore hydrolases like trypsin, which contain serine, histidine and aspartate residue in their catalytic sites, are classified firstly as serine hydrolases (class S), then refined as hydrolases with Ser-His dyad (class S.01) and finally they occupy class S.01.01 (Hydrolases with Ser-His-Asp triad).
Curation method	The main methods of catalytic site annotation are direct literature mining and search of protein three-dimensional structures by templates. To increase reliability of the database only the hydrolases with known 3D structure of catalytic domain are included.
Contact	Igor A. Gariev gariev@hotmail.com

Acknowledgements
Jess program [5] is used for catalytic site search Protein sequences, accession numbers and (partially) names are from UniProt (SwissProt and TrEMBL) [6] database Protein folds are from CATH [7] and SCOP [4] database. Please note, that folds of catalytic domains only are denoted. Many proteins have several domains, for information on folds of non-catalytic domains please refer to the corresponding databases. EC numbers and organisms are from PDB documents [3] and UniProt annotations Catalytic site images are drawn with MolScript [1] and Raster3D [2] programs Trees of proteins properties are drawn on-the-fly with GraphViz software

Acknowledgements

Jess program [5] is used for catalytic site search
Protein sequences, accession numbers and (partially) names are from UniProt (SwissProt and TrEMBL) [6] database
Protein folds are from CATH [7] and SCOP [4] database. Please note, that folds of catalytic domains only are denoted. Many proteins have several domains, for information on folds of non-catalytic domains please refer to the corresponding databases.
EC numbers and organisms are from PDB documents [3] and UniProt annotations
Catalytic site images are drawn with MolScript [1] and Raster3D [2] programs
Trees of proteins properties are drawn on-the-fly with GraphViz software

Useful links
Databases of enzymes' active sites, catalytic mechanisms and classifications of hydrolases Catalytic Site Atlas http://www.ebi.ac.uk/thornton-srv/databases/CSA/ PROCAT - A database of 3D enzyme active site templates http://www.biochem.ucl.ac.uk/bsm/PROCAT/PROCAT.html Structure-Function Linkage Database http://sfld.rbvi.ucsf.edu/ EzCatDB - A Database of Enzyme Catalytic Mechanisms http://mbs.cbrc.jp/EzCatDB/ MACiE - A database of enzyme reaction mechanisms http://www-mitchell.ch.cam.ac.uk/macie/ General-use protein databases UniProt - the Universal Protein Resource (SwissProt database and TrEMBL supplement) http://www.expasy.org/sprot/ PDB - the Protein Data Bank http://www.pdb.org/ Classification of protein folds CATH - Protein Structure Classification (Class, Architecture, Topology and Homologous superfamily) http://cathwww.biochem.ucl.ac.uk/latest/ SCOP - Structural Classification of Proteins http://scop.mrc-lmb.cam.ac.uk/scop/ Classification of hydrolases by sequence similarity CAZY - Carbohydrate-Active enZYmes http://afmb.cnrs-mrs.fr/CAZY/ MEROPS - the Peptidase Database http://merops.sanger.ac.uk/ Homologous protein families Pfam - Protein Families Database http://www.sanger.ac.uk/Software/Pfam/ COG - Clusters of Orthologous Groups of proteins http://www.ncbi.nlm.nih.gov/COG/

Useful links

Databases of enzymes' active sites, catalytic mechanisms and classifications of hydrolases
- Catalytic Site Atlas
  http://www.ebi.ac.uk/thornton-srv/databases/CSA/
- PROCAT - A database of 3D enzyme active site templates
  http://www.biochem.ucl.ac.uk/bsm/PROCAT/PROCAT.html
- Structure-Function Linkage Database
  http://sfld.rbvi.ucsf.edu/
- EzCatDB - A Database of Enzyme Catalytic Mechanisms
  http://mbs.cbrc.jp/EzCatDB/
- MACiE - A database of enzyme reaction mechanisms
  http://www-mitchell.ch.cam.ac.uk/macie/
General-use protein databases
- UniProt - the Universal Protein Resource (SwissProt database and TrEMBL supplement)
  http://www.expasy.org/sprot/
- PDB - the Protein Data Bank
  http://www.pdb.org/
Classification of protein folds
- CATH - Protein Structure Classification (Class, Architecture, Topology and Homologous superfamily)
  http://cathwww.biochem.ucl.ac.uk/latest/
- SCOP - Structural Classification of Proteins
  http://scop.mrc-lmb.cam.ac.uk/scop/
Classification of hydrolases by sequence similarity
- CAZY - Carbohydrate-Active enZYmes
  http://afmb.cnrs-mrs.fr/CAZY/
- MEROPS - the Peptidase Database
  http://merops.sanger.ac.uk/
Homologous protein families
- Pfam - Protein Families Database
  http://www.sanger.ac.uk/Software/Pfam/
- COG - Clusters of Orthologous Groups of proteins
  http://www.ncbi.nlm.nih.gov/COG/

References
Kraulis PJ MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Cryst. (1991). 24, 946-950. doi: 10.1107/S0021889891004399 Merritt EA, Bacon DJ Raster3D: Photorealistic Molecular Graphics. Meth. Enzymol. (1997). 277, 505-524. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic. Acids. Res. (2000). 28 (1), 235-42. pubmed: 10592235 Lo Conte L, Brenner SE, Hubbard TJ, Chothia C, Murzin AG. SCOP database in 2002: refinements accommodate structural genomics. Nucleic. Acids. Res. (2002). 30 (1), 264-7. pubmed: 11752311 Barker JA, Thornton JM. An algorithm for constraint-based structural template matching: application to 3D templates with statistical analysis. Bioinformatics. (2003). 19 (13), 1644-9. pubmed: 12967960 doi: 10.1093/bioinformatics/btg226 Bairoch A, Apweiler R, Wu CH, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, Martin MJ, Natale DA, O'Donovan C, Redaschi N, Yeh LS. The Universal Protein Resource (UniProt). Nucleic. Acids. Res. (2005). 33, D154-9. pubmed: 15608167 doi: 10.1093/nar/gki070 Pearl F, Todd A, Sillitoe I, Dibley M, Redfern O, Lewis T, Bennett C, Marsden R, Grant A, Lee D, Akpor A, Maibaum M, Harrison A, Dallman T, Reeves G, Diboun I, Addou S, Lise S, Johnston C, Sillero A, Thornton J, Orengo C The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis. Nucleic. Acids. Res. (2005). 33, D247-51. pubmed: 15608188

References

Kraulis PJ
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures.
J. Appl. Cryst. (1991). 24, 946-950. doi: 10.1107/S0021889891004399

Merritt EA, Bacon DJ
Raster3D: Photorealistic Molecular Graphics.
Meth. Enzymol. (1997). 277, 505-524.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE.
The Protein Data Bank.
Nucleic. Acids. Res. (2000). 28 (1), 235-42. pubmed: 10592235

Lo Conte L, Brenner SE, Hubbard TJ, Chothia C, Murzin AG.
SCOP database in 2002: refinements accommodate structural genomics.
Nucleic. Acids. Res. (2002). 30 (1), 264-7. pubmed: 11752311

Barker JA, Thornton JM.
An algorithm for constraint-based structural template matching: application to 3D templates with statistical analysis.
Bioinformatics. (2003). 19 (13), 1644-9. pubmed: 12967960 doi: 10.1093/bioinformatics/btg226

Bairoch A, Apweiler R, Wu CH, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, Martin MJ, Natale DA, O'Donovan C, Redaschi N, Yeh LS.
The Universal Protein Resource (UniProt).
Nucleic. Acids. Res. (2005). 33, D154-9. pubmed: 15608167 doi: 10.1093/nar/gki070

Pearl F, Todd A, Sillitoe I, Dibley M, Redfern O, Lewis T, Bennett C, Marsden R, Grant A, Lee D, Akpor A, Maibaum M, Harrison A, Dallman T, Reeves G, Diboun I, Addou S, Lise S, Johnston C, Sillero A, Thornton J, Orengo C
The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis.
Nucleic. Acids. Res. (2005). 33, D247-51. pubmed: 15608188