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2poj

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Revision as of 08:55, 29 August 2018

NMR Solution Structure of the Inhibitor-Free State of Macrophage Metalloelastase (MMP-12)

Structural highlights

2poj is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2oxu, 1jk3, 1jiz
Gene:	MMP12, HME (HUMAN)
Activity:	Macrophage elastase, with EC number 3.4.24.65
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.

Publication Abstract from PubMed

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP-12) appears to exacerbate atherosclerosis, emphysema, aortic aneurysm, rheumatoid arthritis, and inflammatory bowel disease. An inactivating E219A mutation, validated by crystallography and NMR spectra, prevents autolysis of MMP-12 and allows us to determine its NMR structure without an inhibitor. The structural ensemble of the catalytic domain without an inhibitor is based on 2813 nuclear Overhauser effects (NOEs) and has an average RMSD to the mean structure of 0.25 A for the backbone and 0.61 A for all heavy atoms for residues Trp109-Gly263. Compared to crystal structures of MMP-12, helix B (hB) at the active site is unexpectedly more deeply recessed under the beta-sheet. This opens a pocket between hB and beta-strand IV in the active-site cleft. Both hB and an internal cavity are shifted toward beta-strand I, beta-strand III, and helix A on the back side of the protease. About 25 internal NOE contacts distinguish the inhibitor-free solution structure and indicate hB's greater depth and proximity to the sheet and helix A. Line broadening and multiplicity of amide proton NMR peaks from hB are consistent with hB undergoing a slow conformational exchange among subtly different environments. Inhibitor-binding-induced perturbations of the NMR spectra of MMP-1 and MMP-3 map to similar locations across MMP-12 and encompass the internal conformational adjustments. Evolutionary trace analysis suggests a functionally important network of residues that encompasses most of the locations adjusting in conformation, including 18 residues with NOE contacts unique to inhibitor-free MMP-12. The conformational change, sequence analysis, and inhibitor perturbations of NMR spectra agree on the network they identify between structural scaffold and the active site of MMPs.

Solution structure of inhibitor-free human metalloelastase (MMP-12) indicates an internal conformational adjustment.,Bhaskaran R, Palmier MO, Bagegni NA, Liang X, Van Doren SR J Mol Biol. 2007 Dec 14;374(5):1333-44. Epub 2007 Oct 16. PMID:17997411^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bhaskaran R, Palmier MO, Bagegni NA, Liang X, Van Doren SR. Solution structure of inhibitor-free human metalloelastase (MMP-12) indicates an internal conformational adjustment. J Mol Biol. 2007 Dec 14;374(5):1333-44. Epub 2007 Oct 16. PMID:17997411 doi:10.1016/j.jmb.2007.10.028

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2poj"

@@ Line 1: / Line 1: @@
 ==NMR Solution Structure of the Inhibitor-Free State of Macrophage Metalloelastase (MMP-12)==
 <StructureSection load='2poj' size='340' side='right' caption='[[2poj]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2poj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2poj OCA], [http://pdbe.org/2poj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2poj RCSB], [http://www.ebi.ac.uk/pdbsum/2poj PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2poj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2poj OCA], [http://pdbe.org/2poj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2poj RCSB], [http://www.ebi.ac.uk/pdbsum/2poj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2poj ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/po/2poj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/po/2poj_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2poj

From Proteopedia

Revision as of 08:55, 29 August 2018

NMR Solution Structure of the Inhibitor-Free State of Macrophage Metalloelastase (MMP-12)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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