1c8t: Difference between revisions
New page: left|200px<br /> <applet load="1c8t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c8t, resolution 2.60Å" /> '''HUMAN STROMELYSIN-1... |
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[[Image:1c8t.gif|left|200px]]<br /> | [[Image:1c8t.gif|left|200px]]<br /><applet load="1c8t" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1c8t" size=" | |||
caption="1c8t, resolution 2.60Å" /> | caption="1c8t, resolution 2.60Å" /> | ||
'''HUMAN STROMELYSIN-1 (E202Q) CATALYTIC DOMAIN COMPLEXED WITH RO-26-2812'''<br /> | '''HUMAN STROMELYSIN-1 (E202Q) CATALYTIC DOMAIN COMPLEXED WITH RO-26-2812'''<br /> | ||
==Overview== | ==Overview== | ||
Human stromelysin-1 is a member of the matrix metalloproteinase (MMP) | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1C8T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, CA and TR1 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] Full crystallographic information is available from [http:// | 1C8T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=TR1:'>TR1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C8T OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Stromelysin 1]] | [[Category: Stromelysin 1]] | ||
[[Category: Crowther, R | [[Category: Crowther, R L.]] | ||
[[Category: Dunten, P.]] | [[Category: Dunten, P.]] | ||
[[Category: Steele, D | [[Category: Steele, D L.]] | ||
[[Category: el-Kabbani, O.]] | [[Category: el-Kabbani, O.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:03:35 2008'' | ||
Revision as of 13:03, 21 February 2008
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HUMAN STROMELYSIN-1 (E202Q) CATALYTIC DOMAIN COMPLEXED WITH RO-26-2812
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250]
About this StructureAbout this Structure
1C8T is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Stromelysin 1, with EC number 3.4.24.17 Full crystallographic information is available from OCA.
ReferenceReference
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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