1c3i

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{{STRUCTURE_1c3i| PDB=1c3i | SCENE= }}
{{STRUCTURE_1c3i| PDB=1c3i | SCENE= }}
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'''HUMAN STROMELYSIN-1 CATALYTIC DOMAIN COMPLEXED WITH RO-26-2812'''
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===HUMAN STROMELYSIN-1 CATALYTIC DOMAIN COMPLEXED WITH RO-26-2812===
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==Overview==
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Human stromelysin-1 is a member of the matrix metalloproteinase (MMP) family of enzymes. The active site glutamic acid of the MMPs is conserved throughout the family and plays a pivotal role in the catalytic mechanism. The structural and functional consequences of a glutamate to glutamine substitution in the active site of stromelysin-1 were investigated in this study. In contrast to the wild-type enzyme, the glutamine-substituted mutant was not active in a zymogram assay where gelatin was the substrate, was not activated by organomercurials and showed no activity against a peptide substrate. The glutamine-substituted mutant did, however, bind to TIMP-1, the tissue inhibitor of metalloproteinases, after cleavage of the propeptide with trypsin. A second construct containing the glutamine substitution but lacking the propeptide was also inactive in the proteolysis assays and capable of TIMP-1 binding. X-ray structures of the wild-type and mutant proteins complexed with the propeptide-based inhibitor Ro-26-2812 were solved and in both structures the inhibitor binds in an orientation the reverse of that of the propeptide in the pro-form of the enzyme. The inhibitor makes no specific interactions with the active site glutamate and a comparison of the wild-type and mutant structures revealed no major structural changes resulting from the glutamate to glutamine substitution.
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{{ABSTRACT_PUBMED_10877850}}
==About this Structure==
==About this Structure==
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[[Category: Steele, D L.]]
[[Category: Steele, D L.]]
[[Category: Stromelysin-1]]
[[Category: Stromelysin-1]]
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Revision as of 17:09, 30 June 2008

Image:1c3i.png

Template:STRUCTURE 1c3i

HUMAN STROMELYSIN-1 CATALYTIC DOMAIN COMPLEXED WITH RO-26-2812

Template:ABSTRACT PUBMED 10877850

About this Structure

1C3I is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Expression, characterization and structure determination of an active site mutant (Glu202-Gln) of mini-stromelysin-1., Steele DL, El-Kabbani O, Dunten P, Windsor LJ, Kammlott RU, Crowther RL, Michoud C, Engler JA, Birktoft JJ, Protein Eng. 2000 Jun;13(6):397-405. PMID:10877850

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