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[[Image:1jiz.gif|left|200px]]


{{Structure
==Crystal Structure Analysis of human Macrophage Elastase MMP-12==
|PDB= 1jiz |SIZE=350|CAPTION= <scene name='initialview01'>1jiz</scene>, resolution 2.60&Aring;
<StructureSection load='1jiz' size='340' side='right'caption='[[1jiz]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
|SITE=
== Structural highlights ==
|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>
<table><tr><td colspan='2'>[[1jiz]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JIZ FirstGlance]. <br>
|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]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CGS:N-HYDROXY-2(R)-[[(4-METHOXYPHENYL)SULFONYL](3-PICOLYL)AMINO]-3-METHYLBUTANAMIDE+HYDROCHLORIDE'>CGS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jiz OCA], [https://pdbe.org/1jiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jiz RCSB], [https://www.ebi.ac.uk/pdbsum/1jiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jiz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ji/1jiz_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1jiz ConSurf].
<div style="clear:both"></div>


'''Crystal Structure Analysis of human Macrophage Elastase MMP-12'''
==See Also==
 
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 
__TOC__
==Overview==
</StructureSection>
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.
 
==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, 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==
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==
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: Large Structures]]
[[Category: Single protein]]
[[Category: Bauer MMT]]
[[Category: Bauer, M M.T.]]
[[Category: Dollinger H]]
[[Category: Dollinger, H.]]
[[Category: Jung B]]
[[Category: Jung, B.]]
[[Category: Nar H]]
[[Category: Nar, H.]]
[[Category: Werle K]]
[[Category: Werle, K.]]
[[Category: CA]]
[[Category: CGS]]
[[Category: ZN]]
[[Category: chronic obstructive pulmonary disease]]
[[Category: matrix metalloproteinase]]
[[Category: mmp-12]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:04:13 2008''

Latest revision as of 10:39, 7 February 2024

Crystal Structure Analysis of human Macrophage Elastase MMP-12Crystal Structure Analysis of human Macrophage Elastase MMP-12

Structural highlights

1jiz is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MMP12_HUMAN May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1jiz, resolution 2.60Å

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