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Structures of complexes of rhizopuspepsin with pepstatin and other statine‐containing inhibitors
Author(s) -
Suguna Kaza,
Padlan Eduardo A.,
Bott Richard,
Boger Joshua,
Parris Kevin D.,
Davies David R.
Publication year - 1992
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/prot.340130303
Subject(s) - pepstatin , scissile bond , chemistry , stereochemistry , molecule , hydrogen bond , residue (chemistry) , active site , peptide bond , enzyme , enzyme inhibitor , biochemistry , protease , organic chemistry
The three‐dimensional structures of the complexes of the aspartic proteinase from Rhizopus chinensis (Rhizopuspepsin, EC 3.4.23.6) with pepstatin and two pepstatin like peptide inhibitors of renin have been detrmined by X‐ray diffraction methods and refined by restrained least‐squares procedures. The inhibitors adopt an extended conformation and lie in the deep groove located between the two domains of the enzyme. Inhibitor binding is accompanied by a conformational change at the “flap,” a β‐hairpin loop regions, that projects over the binding cleft andcloses down over the inhibitor, excluding water molecules from the vicinityof the scissile bond. The hydroxyl group of the central statyl residue of the inhibitors replaces the water molecule found between the two active aspartates, Asp‐35 and Asp‐218, in the native structure. The refined structures provide additional data to define the specific subsites of the enzyme and also show a system of hydrogen bonding to the inhibitor backbone similar to that observed for a reduced inhibitor. Published 1992 Wiley‐Liss, Inc.