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Hydrolase/hydrolase inhibitor
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PDB id
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1c8t
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.24.17
- Stromelysin 1.
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Reaction:
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Preferential cleavage where P1', P2' and P3' are hydrophobic residues.
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Cofactor:
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Calcium; Zinc
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular matrix
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1 term
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Biological process
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proteolysis
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1 term
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Biochemical function
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metallopeptidase activity
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3 terms
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DOI no:
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Protein Eng
13:397-405
(2000)
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PubMed id:
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Expression, characterization and structure determination of an active site mutant (Glu202-Gln) of mini-stromelysin-1.
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D.L.Steele,
O.El-Kabbani,
P.Dunten,
L.J.Windsor,
R.U.Kammlott,
R.L.Crowther,
C.Michoud,
J.A.Engler,
J.J.Birktoft.
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ABSTRACT
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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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R.Bhaskaran,
M.O.Palmier,
N.A.Bagegni,
X.Liang,
and
S.R.Van Doren
(2007).
Solution structure of inhibitor-free human metalloelastase (MMP-12) indicates an internal conformational adjustment.
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J Mol Biol, 374,
1333-1344.
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PDB code:
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M.Peñalver-Mellado,
F.García-Heras,
S.Padmanabhan,
D.García-Moreno,
F.J.Murillo,
and
M.Elías-Arnanz
(2006).
Recruitment of a novel zinc-bound transcriptional factor by a bacterial HMGA-type protein is required for regulating multiple processes in Myxococcus xanthus.
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Mol Microbiol, 61,
910-926.
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H.Yi,
J.Gruszczynska-Biegala,
D.Wood,
Z.Zhao,
and
A.Zolkiewska
(2005).
Cooperation of the metalloprotease, disintegrin, and cysteine-rich domains of ADAM12 during inhibition of myogenic differentiation.
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J Biol Chem, 280,
23475-23483.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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