Update 1 of: Proteases universally recognize beta strands in their active sites

Madala, Praveen K., Tyndall, Joel D. A., Nall, Tessa and Fairlie, David P. (2010) Update 1 of: Proteases universally recognize beta strands in their active sites. Chemical Reviews, 110 4: 1-33. doi:10.1021/cr900368a

Author Madala, Praveen K.
Tyndall, Joel D. A.
Nall, Tessa
Fairlie, David P.
Title Update 1 of: Proteases universally recognize beta strands in their active sites
Journal name Chemical Reviews   Check publisher's open access policy
ISSN 0009-2665
Publication date 2010-06-09
Year available 2010
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1021/cr900368a
Volume 110
Issue 4
Start page 1
End page 33
Total pages 33
Place of publication Washington, DC, U.S.A.
Publisher American Chemical Society
Collection year 2011
Language eng
Formatted abstract
Among proteases or proteinases, the endopeptidases account for a significant proportion (∼2%) of the human genome with over 550 defined members and a further 100 or so predicted human proteases. Proteases also represent 1−5% of the genomes of infectious organisms such as bacteria, parasites, and viruses. They are categorized by the nature of their active-site catalytic residue as metallo (34%), serine (30%), cysteine (26%), aspartic/glutamate (4%), and the less characterized threonine (5%). Proteases have been assembled into families based on structural and catalytic homology, further categorized into families according to sequence homology, and localized to specific chromosomes at least for the human genome.

This review summarizes an analysis of over 1500 three-dimensional crystal (X-ray) and solution (NMR) structures from the PDB of substrates, products, and inhibitors bound in the active sites of aspartic, serine, metallo, cysteine, and threonine endopeptidases. The active sites of all five protease classes were found to recognize peptidic and nonpeptidic ligands in an extended beta strand conformation, with few exceptions. Comparisons of protease-bound ligand conformations are illustrated by structural superpositions for a subset of structures, including 27 aspartic (239 inhibitors), 56 serine (305 inhibitors), 29 metallo (152 inhibitors), 31 cysteine (129 inhibitor complexes), and 4 threonine (8 inhibitor complexes) proteases, among the protease−ligand structures that we have analyzed. The extended substrate-binding mode is also illustrated for 6 aspartic proteases (19 substrates), 2 serine proteases, 2 cysteine proteases, and 1 metalloprotease.
Keyword β-Strands
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes This is a Chemical Reviews Perennial Review. The root paper of this title was published in Chem. Rev. 2005, 105 (3), 973−1000; Published (Web) Feb. 16, 2005. Updates to the text appear in red type.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Created: Tue, 08 Feb 2011, 12:25:24 EST by Susan Allen on behalf of Institute for Molecular Bioscience