1jiz: Difference between revisions
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[[Image:1jiz.gif|left|200px]] | [[Image:1jiz.gif|left|200px]] | ||
'''Crystal Structure Analysis of human Macrophage Elastase MMP-12''' | {{Structure | ||
|PDB= 1jiz |SIZE=350|CAPTION= <scene name='initialview01'>1jiz</scene>, resolution 2.60Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=CGS:N-HYDROXY-2(R)-[[(4-METHOXYPHENYL)SULFONYL](3-PICOLYL)AMINO]-3-METHYLBUTANAMIDE HYDROCHLORIDE'>CGS</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] | |||
|GENE= | |||
}} | |||
'''Crystal Structure Analysis of human Macrophage Elastase MMP-12''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1JIZ is a [ | 1JIZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JIZ OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor., Nar H, Werle K, Bauer MM, Dollinger H, Jung B, J Mol Biol. 2001 Sep 28;312(4):743-51. PMID:[http:// | Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor., Nar H, Werle K, Bauer MM, Dollinger H, Jung B, J Mol Biol. 2001 Sep 28;312(4):743-51. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11575929 11575929] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Macrophage elastase]] | [[Category: Macrophage elastase]] | ||
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[[Category: mmp-12]] | [[Category: mmp-12]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:04:13 2008'' | ||
Revision as of 13:04, 20 March 2008
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| , resolution 2.60Å | |||||||
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| Ligands: | , and | ||||||
| Activity: | Macrophage elastase, with EC number 3.4.24.65 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure Analysis of human Macrophage Elastase MMP-12
OverviewOverview
Human macrophage elastase (MMP-12) is a member of the family of matrix metalloproteinases (MMPs) that plays, like other members of the family, an important role in inflammatory processes contributing to tissue remodelling and destruction. In particular, a prominent role of MMP-12 in the destruction of elastin in the lung alveolar wall and the pathogenesis of emphysema has been suggested. It is therefore an attractive therapeutic target. We describe here the crystal structure of the catalytic domain of MMP-12 in complex with a hydroxamic acid inhibitor, CGS27023A. MMP-12 adopts the typical MMP fold and binds a structural zinc ion and three calcium ions in addition to the catalytic zinc ion. The enzyme structure shows an ordered N terminus close to the active site that is identical in conformation with the superactivated form of MMP-8. The S1'-specificity pocket is large and extends into a channel through the protein, which puts MMP-12 into the class of MMPs 3, 8 and 13 with large and open specificity pockets. The two crystallographically independent molecules adopt different conformations of the S1'-loop and its neighbouring loop due to differing crystal packing environments, suggesting that flexibility or the possibility of structural adjustments of these loop segments are intrinsic features of the MMP-12 structure and probably a common feature for all MMPs. The inhibitor binds in a bidentate fashion to the catalytic zinc ion. Its polar groups form hydrogen bonds in a substrate-like manner with beta-strand sIV of the enzyme, while the hydrophobic substituents are either positioned on the protein surface and are solvent-exposed or fill the upper part of the specificity pocket. The present structure enables us to aid the design of potent and selective inhibitors for MMP-12.
DiseaseDisease
Known diseases associated with this structure: Cardiomyopathy, dilated, 1G OMIM:[188840], Cardiomyopathy, familial hypertrophic OMIM:[188840], Muscular dystrophy, limb-girdle, type 2J OMIM:[188840], Myopathy, early-onset, with fatal cardiomyopathy OMIM:[188840], Myopathy, proximal, with early respiratory muscle involvement OMIM:[188840], Tibial muscular dystrophy, tardive OMIM:[188840]
About this StructureAbout this Structure
1JIZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor., Nar H, Werle K, Bauer MM, Dollinger H, Jung B, J Mol Biol. 2001 Sep 28;312(4):743-51. PMID:11575929
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