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Crystal Structure of an Ecotin−Collagenase Complex Suggests a Model for Recognition and Cleavage of the Collagen Triple Helix†
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Section:Abstract
The crystal structure of fiddler crab collagenase complexed with the dimeric serine protease inhibitor ecotin at 2.5 Å resolution reveals an extended cleft providing binding sites for at least 11 contiguous substrate residues. Comparison of the positions of nine intermolecular main chain hydrogen bonding interactions in the cleft, with the known sequences at the cleavage site of type I collagen, suggests that the protease binding loop of ecotin adopts a conformation mimicking that of the cleaved strand of collagen. A well-defined groove extending across the binding surface of the enzyme readily accommodates the two other polypeptide chains of the triple-helical substrate. These observations permit construction of a detailed molecular model for collagen recognition and cleavage by this invertebrate serine protease. Ecotin undergoes a pronounced internal structural rearrangement which permits binding in the observed conformation. The capacity for such rearrangement appears to be a key determinant of its ability to inhibit a wide range of serine proteases.
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This article has been cited by 6 ACS Journal articles (5 most recent appear below).
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Domain Structure of the Staphylococcus aureus Collagen Adhesin
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Kathlynn C. Brown, Zhonghua Yu, Alma L. Burlingame, and Charles S. CraikBiochemistry1998 37 (13), 4397-4406The Ni(II) complex of the tripeptide NH2-glycine-glycine-histidine-COOH (GGH) mediates efficient protein−protein cross-linking in the presence of oxidants such as oxone and monoperoxyphthalic acid (MMPP). Here we demonstrate that GGH fused to the amino ...
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History
- Published In Issue May 06, 1997
- Received July 17, 1996
Revised Manuscript Received December 10, 1996
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