1jk3: Difference between revisions
New page: left|200px<br /> <applet load="1jk3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jk3, resolution 1.09Å" /> '''Crystal structure o... |
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[[Image:1jk3. | [[Image:1jk3.jpg|left|200px]]<br /><applet load="1jk3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1jk3, resolution 1.09Å" /> | caption="1jk3, resolution 1.09Å" /> | ||
'''Crystal structure of human MMP-12 (Macrophage Elastase) at true atomic resolution'''<br /> | '''Crystal structure of human MMP-12 (Macrophage Elastase) at true atomic resolution'''<br /> | ||
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==Disease== | ==Disease== | ||
Known diseases associated with this structure: Cardiomyopathy, dilated, 1G OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Cardiomyopathy, familial hypertrophic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Muscular dystrophy, limb-girdle, type 2J OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Myopathy, proximal, with early respiratory muscle involvement OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Tibial muscular dystrophy, tardive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]] | Known diseases associated with this structure: Cardiomyopathy, dilated, 1G OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Cardiomyopathy, familial hypertrophic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Muscular dystrophy, limb-girdle, type 2J OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Myopathy, early-onset, with fatal cardiomyopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Myopathy, proximal, with early respiratory muscle involvement OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Tibial muscular dystrophy, tardive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]] | ||
==About this Structure== | ==About this Structure== | ||
1JK3 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 BAT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1JK3 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=BAT:'>BAT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JK3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: mmp12]] | [[Category: mmp12]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:07:42 2008'' | ||
Revision as of 17:07, 15 February 2008
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Crystal structure of human MMP-12 (Macrophage Elastase) at true atomic resolution
OverviewOverview
The macrophage elastase enzyme (MMP-12) expressed mainly in alveolar, macrophages has been identified in the mouse lung as the main destructive, agent associated with cigarette smoking, which gives rise to emphysema, both directly via elastin degradation and indirectly by disturbing the, proteinase/antiproteinase balance via inactivation of the, alpha1-proteinase inhibitor (alpha1-PI), the antagonist of the leukocyte, elastase. The catalytic domain of human recombinant MMP-12 has been, crystallized in complex with the broad-specificity inhibitor batimastat, (BB-94). The crystal structure analysis of this complex, determined using, X-ray data to 1.1 A and refined to an R-value of 0.165, reveals an overall, fold similar to that of other MMPs. However, the S-shaped double loop, connecting strands III and IV is fixed closer to the beta-sheet and, projects its His172 side-chain further into the rather hydrophobic, active-site cleft, defining the S3 and the S1-pockets and separating them, from each other to a larger extent than is observed in other MMPs. The, S2-site is planar, while the characteristic S1'-subsite is a continuous, tube rather than a pocket, in which the MMP-12-specific Thr215 replaces a, Val residue otherwise highly conserved in almost all other MMPs. This, alteration might allow MMP-12 to accept P1' Arg residues, making it unique, among MMPs. The active-site cleft of MMP-12 is well equipped to bind and, efficiently cleave the AlaMetPhe-LeuGluAla sequence in the reactive-site, loop of alpha1-PI, as occurs experimentally. Similarities in contouring, and particularly a common surface hydrophobicity both inside and distant, from the active-site cleft explain why MMP-12 shares many substrates with, matrilysin (MMP-7). The MMP-12 structure is an excellent template for the, structure-based design of specific inhibitors for emphysema therapy and, for the construction of mutants to clarify the role of this MMP.
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
1JK3 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Macrophage elastase, with EC number 3.4.24.65 Full crystallographic information is available from OCA.
ReferenceReference
Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure., Lang R, Kocourek A, Braun M, Tschesche H, Huber R, Bode W, Maskos K, J Mol Biol. 2001 Sep 28;312(4):731-42. PMID:11575928
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