Releasing the Spring Cofactor- and Substrate-assisted Activation of Factor IXa

Releasing the Spring Cofactor- and Substrate-assisted Activation of Factor IXa 

Copyright (g) 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31184-X 

In an attempt to understand this unique behavior of flXa, we hnk enzymatic and structural properties. Here, we review the substrate preferences of flXa and homologous enzymes, and relate them to stractural elements critical for substrate recognition. 

Of particular interest, the conformation of the flXa 99-loop (chymotrypsinogen numbering used throughout within the serine protease domain) deviates considerably from those observed in the related enzymes of the fix gene family [10-14]. Kolkman and Mertens further demonstrated that the 99-loop restricts enzymatic 

The side-chain of Tyr99 adopts different conformations in the two crystal structures of nXa reported to date [11, 16], In both structures Tyr99 is in steric conflict with canonical substrate binding in the S2-S4 sites. These observations suggest a critical role of Tyr99 and spatially neighboring amino acids in the substrate-dependent activity of nXa. In particular, Lys98 is likely to electrostatically interfere with the basic substrate preference of fiXa. 

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