PMID: 9443338Jan 27, 1998Paper

Conserved water molecules in the specificity pocket of serine proteases and the molecular mechanism of Na+ binding

Proteins
M M Krem, E Di Cera

Abstract

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.

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Citations

Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·K F AhmadG G Privé
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·E R GuintoE Di Cera
Mar 19, 1999·Protein Science : a Publication of the Protein Society·A Vindigni, E Di Cera
Dec 5, 2015·The Journal of Physical Chemistry. B·Ikuo KurisakiMasataka Nagaoka
Mar 11, 2008·Molecular Aspects of Medicine·Enrico Di Cera
May 1, 2005·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·Paolo AscenziFabio Polticelli
May 16, 2006·Proteins·Christopher A BottomsJohn J Tanner
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May 21, 2004·The Journal of Biological Chemistry·Agustin O PinedaEnrico Di Cera
Feb 20, 2019·Chemistry : a European Journal·Collin T Zahler, Bryan F Shaw
Mar 10, 2007·Physical Chemistry Chemical Physics : PCCP·Enrico Di CeraLaura C Garvey
Sep 25, 1999·The Journal of Biological Chemistry·M M KremE Di Cera
May 8, 2010·The Journal of Physical Chemistry. B·Hannes G WallnoeferThomas Fox
Apr 26, 2001·Biophysical Chemistry·N Griffon, E Di Stasio
Feb 18, 2010·Journal of Chemical Information and Modeling·Ramasamy Thilagavathi, Ricardo L Mancera
May 6, 2017·Journal of Medicinal Chemistry·Francesca SpyrakisGlen E Kellogg

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