Premium
1.56 Å structure of mature truncated human fibroblast collagenase
Author(s) -
Spurlino John C.,
Smallwood Angela M.,
Carlton Dennis D.,
Banks Tracey M.,
Vavra Karen J.,
Johnson Jeffrey S.,
Cook Ewell R.,
Falvo Joseph,
Wahl Robert C.,
Pulvino Tricia A.,
Wendoloski John J.,
Smith Douglas L.
Publication year - 1994
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.340190203
Subject(s) - thermolysin , collagenase , matrix metalloproteinase , chemistry , enzyme , cleavage (geology) , fibroblast , zinc , active site , stereochemistry , binding site , peptide , biochemistry , trypsin , biology , in vitro , paleontology , organic chemistry , fracture (geology)
The X‐ray crystal structure of a 19 kDa active fragment of human fibroblast collagenase has been determined by the multiple isomorphous replacement method and refined at 1.56 Å resolution to an R ‐factor of 17.4%. The current structure includes a bound hydroxamate inhibitor, 88 waters and three metal atoms (two zincs and a calcium). The overall topology of the enzyme, comprised of a five stranded β‐sheet and three α‐helices, is similar to the thermolysin‐like metalloproteinases. There are some important differences between the collagenase and thermolysin families of enzymes. The active site zinc ligands are all histidines (His‐218, His‐222, and His‐228). The presence of a second zinc ion in a structural role is a unique feature of the matrix metalloproteinases. The binding properties of the active site cleft are more dependent on the main chain conformation of the enzyme (and substrate) compared with thermolysin. A mechanism of action for peptide cleavage similar to that of thermolysin is proposed for fibroblast collagenase. © 1994 Wiley‐Liss, Inc.