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4h84

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Revision as of 16:06, 17 May 2017

Crystal structure of the catalytic domain of Human MMP12 in complex with a selective carboxylate based inhibitor.

Structural highlights

4h84 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	4h30, 4h49, 4h76, 3ts4, 3tsk, 4efs, 4h82
Gene:	HME, MMP12 (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.

Publication Abstract from PubMed

Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects.

Crystallization of bi-functional ligand protein complexes.,Antoni C, Vera L, Devel L, Catalani MP, Czarny B, Cassar-Lajeunesse E, Nuti E, Rossello A, Dive V, Stura EA J Struct Biol. 2013 Apr 6. pii: S1047-8477(13)00086-5. doi:, 10.1016/j.jsb.2013.03.015. PMID:23567804^[1]

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

References

↑ Antoni C, Vera L, Devel L, Catalani MP, Czarny B, Cassar-Lajeunesse E, Nuti E, Rossello A, Dive V, Stura EA. Crystallization of bi-functional ligand protein complexes. J Struct Biol. 2013 Apr 6. pii: S1047-8477(13)00086-5. doi:, 10.1016/j.jsb.2013.03.015. PMID:23567804 doi:10.1016/j.jsb.2013.03.015

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4h84"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the catalytic domain of Human MMP12 in complex with a selective carboxylate based inhibitor.==
 <StructureSection load='4h84' size='340' side='right' caption='[[4h84]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HME, MMP12 ([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=4h84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h84 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h84 RCSB], [http://www.ebi.ac.uk/pdbsum/4h84 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=4h84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h84 OCA], [http://pdbe.org/4h84 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h84 RCSB], [http://www.ebi.ac.uk/pdbsum/4h84 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h84 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4h84" style="background-color:#fffaf0;"></div>
 ==See Also==

4h84

From Proteopedia

Revision as of 16:06, 17 May 2017

Crystal structure of the catalytic domain of Human MMP12 in complex with a selective carboxylate based inhibitor.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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