Premium
Conserved water molecules in the specificity pocket of serine proteases and the molecular mechanism of Na + binding
Author(s) -
Krem Maxwell M.,
Di Cera Enrico
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19980101)30:1<34::aid-prot3>3.0.co;2-k
Subject(s) - proteases , thrombin , chemistry , trypsin , biochemistry , serine , serine protease , protease , enzyme , binding site , biology , platelet , immunology
Conservation of clusters of buried water molecules is a structural motif present throughout the serine protease family. Frequently, these clusters are shaped as water channels forming extensive hydrogen‐bonding networks linked to the protein backbone. The most conspicuous example is the water channel present in the specificity pocket of trypsin and thrombin. In thrombin, other vitamin K‐dependent proteases, and some complement factors, Na + binds in this water channel and enhances allosterically the catalytic activity of the enzyme, whereas digestive and fibrinolytic proteases are devoid of such regulation. A comparative analysis of proteases with and without Na + binding capability reveals the role of the water channel in maintaining the structural organization of the specificity pocket and in Na + coordination. This enables the formulation of a molecular mechanism for Na + binding in thrombin and leads to the identification of the structural changes necessary to engineer a functional Na + site and enhanced catalytic activity in trypsin and other proteases. Proteins 30:34–42, 1998. © 1998 Wiley‐Liss, Inc.