4h82 - Revision history

OCA at 15:01, 20 September 2023

OCA — Wed, 20 Sep 2023 15:01:23 GMT

←Older revision		Revision as of 15:01, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4h82]] is a 4 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=4H82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H82 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4h82]] is a 4 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=4H82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H82 FirstGlance]. <br>
-	</td></tr><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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L29:N,N-BIS(2-{(BIPHENYL-4-YLSULFONYL)[(2R)-1-(HYDROXYAMINO)-3-METHYL-1-OXOBUTAN-2-YL]AMINO}ETHYL)BENZENE-1,3-DICARBOXAMIDE+(NON-PREFERRED+NAME)'>L29</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.9Å</td></tr>
		+	<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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L29:N,N-BIS(2-{(BIPHENYL-4-YLSULFONYL)[(2R)-1-(HYDROXYAMINO)-3-METHYL-1-OXOBUTAN-2-YL]AMINO}ETHYL)BENZENE-1,3-DICARBOXAMIDE+(NON-PREFERRED+NAME)'>L29</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</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=4h82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h82 OCA], [https://pdbe.org/4h82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h82 RCSB], [https://www.ebi.ac.uk/pdbsum/4h82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h82 ProSAT]</span></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=4h82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h82 OCA], [https://pdbe.org/4h82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h82 RCSB], [https://www.ebi.ac.uk/pdbsum/4h82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h82 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:04, 3 November 2022

OCA — Thu, 03 Nov 2022 08:04:28 GMT

←Older revision		Revision as of 08:04, 3 November 2022
Line 1:		Line 1:

	==Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.==		==Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.==
-	<StructureSection load='4h82' size='340' side='right' caption='[[4h82]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='4h82' size='340' side='right'caption='[[4h82]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4h82]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H82 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4H82 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4h82]] is a 4 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=4H82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H82 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L29:N,N-BIS(2-{(BIPHENYL-4-YLSULFONYL)[(2R)-1-(HYDROXYAMINO)-3-METHYL-1-OXOBUTAN-2-YL]AMINO}ETHYL)BENZENE-1,3-DICARBOXAMIDE+(NON-PREFERRED+NAME)'>L29</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene~~></td></tr>~~	+	</td></tr><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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L29:N,N-BIS(2-{(BIPHENYL-4-YLSULFONYL)[(2R)-1-(HYDROXYAMINO)-3-METHYL-1-OXOBUTAN-2-YL]AMINO}ETHYL)BENZENE-1,3-DICARBOXAMIDE+(NON-PREFERRED+NAME)'>L29</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4h30\|4h30]], [[4h2e\|4h2e]], [[4h1q\|4h1q]], [[4h49\|4h49]], [[4h3x\|4h3x]], [[4h84\|4h84]]</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=4h82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h82 OCA], [https://pdbe.org/4h82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h82 RCSB], [https://www.ebi.ac.uk/pdbsum/4h82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h82 ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CLG4B, MMP9 ([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/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] </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=4h82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h82 OCA], [~~http~~://pdbe.org/4h82 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4h82 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4h82 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4h82 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:[~~http~~://omim.org/entry/603932 603932]]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.<ref>PMID:18455130</ref> Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:[~~http~~://omim.org/entry/613073 613073]]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.	+	[https://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:[https://omim.org/entry/603932 603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.<ref>PMID:18455130</ref> Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:[https://omim.org/entry/613073 613073]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-\|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref>	+	[https://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-\|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
-	*[[Matrix metalloproteinase\|Matrix metalloproteinase]]	+	*[[Matrix metalloproteinase 3D structures\|Matrix metalloproteinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Gelatinase B~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Antoni, C]]	+	[[Category: Antoni C]]
-	[[Category: Cassar-Lajeunesse, E]]	+	[[Category: Cassar-Lajeunesse E]]
-	[[Category: Dive, V]]	+	[[Category: Dive V]]
-	[[Category: Nuti, E]]	+	[[Category: Nuti E]]
-	[[Category: Rossello, A]]	+	[[Category: Rossello A]]
-	[[Category: Stura~~, E A~~]]	+	[[Category: Stura EA]]
-	[[Category: Vera, L]]	+	[[Category: Vera L]]
-	~~[[Category: Gelatinase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Hydrolase/twin inhibitor]]~~	+
-	~~[[Category: Zincin-like~~]]	+

OCA at 16:09, 17 May 2017

OCA — Wed, 17 May 2017 16:09:28 GMT

←Older revision		Revision as of 16:09, 17 May 2017
Line 1:		Line 1:
		+
	==Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.==		==Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.==
	<StructureSection load='4h82' size='340' side='right' caption='[[4h82]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4h82' size='340' side='right' caption='[[4h82]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CLG4B, MMP9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CLG4B, MMP9 ([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/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] </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=4h82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h82 RCSB], [http://www.ebi.ac.uk/pdbsum/4h82 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=4h82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h82 OCA], [http://pdbe.org/4h82 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h82 RCSB], [http://www.ebi.ac.uk/pdbsum/4h82 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h82 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4h82" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:44, 12 August 2015

OCA — Wed, 12 Aug 2015 08:44:39 GMT

←Older revision		Revision as of 08:44, 12 August 2015
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Starting from~~ the ~~observation that the CbzNH(CH2)2 side chain~~ of the ~~potent MMP-2/MMP-14 inhibitor~~, ~~benzyl~~-~~(3R)~~-4-~~(hydroxyamino)-3-[isopropoxy(1~~,~~1'-biphenyl-4-yl-sulfonyl)amino]-4-o xobutylcarbamate~~, ~~(R)-1 lies in a hydrophobic region (S1) exposed~~ to the ~~solvent of the protease active site~~, we ~~hypothesized~~ that ~~an aminoethylcarboxamido chain structurally related~~ to that ~~of (R)~~-~~1 might be an useful tool~~ to ~~bind another linker stretching out from~~ the ~~protein. This would be able~~ to ~~interact either with a~~ enzyme ~~region adjacent to the active site, or with other molecules~~ of ~~matrix metalloproteinases (MMPs), or other proteins~~ of the ~~extracellular matrix (ECM) that may~~ be ~~involved in~~ the ~~enzyme activation. On these basis we describe new dimeric compounds of type 2, twin hydroxamic acids, obtained~~ by the ~~joint~~ of ~~two drug entities of (R)~~-~~1 linked in P1 by extendable semirigid linkers~~. ~~Type 2 compounds are potentially able to undergo more complex inhibitor~~-~~enzyme interactions than those occurring with monomeric compounds of type 1, thus influencing positively~~ the ~~potency, selectivity and/or cytotoxicity~~ of ~~the new compounds~~.	+	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.

-	~~A new development of matrix metalloproteinase inhibitors: twin hydroxamic acids as potent inhibitors~~ of ~~MMPs~~.,~~Rossello A~~, ~~Nuti E~~, Catalani MP, ~~Carelli P~~, ~~Orlandini~~ E, ~~Rapposelli S~~, ~~Tuccinardi T~~, ~~Atkinson SJ~~, ~~Murphy G, Balsamo A Bioorg Med Chem Lett~~. ~~2005 May 2;15~~(9)~~:2311~~-4. PMID:~~15837315~~<ref>PMID:~~15837315~~</ref>	+	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<ref>PMID:23567804</ref>

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

OCA at 08:04, 25 January 2015

OCA — Sun, 25 Jan 2015 08:04:44 GMT

←Older revision		Revision as of 08:04, 25 January 2015
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	[[Category: Gelatinase B]]		[[Category: Gelatinase B]]
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Antoni, C.]]	+	[[Category: Antoni, C]]
-	[[Category: Cassar-Lajeunesse, E.]]	+	[[Category: Cassar-Lajeunesse, E]]
-	[[Category: Dive, V.]]	+	[[Category: Dive, V]]
-	[[Category: Nuti, E.]]	+	[[Category: Nuti, E]]
-	[[Category: Rossello, A.]]	+	[[Category: Rossello, A]]
-	[[Category: Stura, E A.]]	+	[[Category: Stura, E A]]
-	[[Category: Vera, L.]]	+	[[Category: Vera, L]]
	[[Category: Gelatinase]]		[[Category: Gelatinase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Hydrolase/twin inhibitor]]		[[Category: Hydrolase/twin inhibitor]]
	[[Category: Zincin-like]]		[[Category: Zincin-like]]

OCA at 11:30, 22 October 2014

OCA — Wed, 22 Oct 2014 11:30:41 GMT

←Older revision		Revision as of 11:30, 22 October 2014
Line 21:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+
		+	==See Also==
		+	*[[Matrix metalloproteinase\|Matrix metalloproteinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:49, 20 October 2014

OCA — Mon, 20 Oct 2014 08:49:15 GMT

←Older revision		Revision as of 08:49, 20 October 2014
Line 21:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
-
-	==See Also==
-	*[[Matrix metalloproteinase\|Matrix metalloproteinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:50, 8 October 2014

OCA — Wed, 08 Oct 2014 05:50:38 GMT

←Older revision		Revision as of 05:50, 8 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4h82\| PDB=4h82 \| SCENE= }}~~	+	==Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.==
-	===Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.===	+	<StructureSection load='4h82' size='340' side='right' caption='[[4h82]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	{~~{ABSTRACT_PUBMED_15837315}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4h82]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H82 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=L29:N,N-BIS(2-{(BIPHENYL-4-YLSULFONYL)[(2R)-1-(HYDROXYAMINO)-3-METHYL-1-OXOBUTAN-2-YL]AMINO}ETHYL)BENZENE-1,3-DICARBOXAMIDE+(NON-PREFERRED+NAME)'>L29</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PPI:PROPANOIC+ACID'>PPI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4h30\|4h30]], [[4h2e\|4h2e]], [[4h1q\|4h1q]], [[4h49\|4h49]], [[4h3x\|4h3x]], [[4h84\|4h84]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CLG4B, MMP9 ([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/Gelatinase_B Gelatinase B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.35 3.4.24.35] </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=4h82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h82 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h82 RCSB], [http://www.ebi.ac.uk/pdbsum/4h82 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:[http://omim.org/entry/603932 603932]]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.<ref>PMID:18455130</ref> Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:[http://omim.org/entry/613073 613073]]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.		[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:[http://omim.org/entry/603932 603932]]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.<ref>PMID:18455130</ref> Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:[http://omim.org/entry/613073 613073]]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-\|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Starting from the observation that the CbzNH(CH2)2 side chain of the potent MMP-2/MMP-14 inhibitor, benzyl-(3R)-4-(hydroxyamino)-3-[isopropoxy(1,1'-biphenyl-4-yl-sulfonyl)amino]-4-o xobutylcarbamate, (R)-1 lies in a hydrophobic region (S1) exposed to the solvent of the protease active site, we hypothesized that an aminoethylcarboxamido chain structurally related to that of (R)-1 might be an useful tool to bind another linker stretching out from the protein. This would be able to interact either with a enzyme region adjacent to the active site, or with other molecules of matrix metalloproteinases (MMPs), or other proteins of the extracellular matrix (ECM) that may be involved in the enzyme activation. On these basis we describe new dimeric compounds of type 2, twin hydroxamic acids, obtained by the joint of two drug entities of (R)-1 linked in P1 by extendable semirigid linkers. Type 2 compounds are potentially able to undergo more complex inhibitor-enzyme interactions than those occurring with monomeric compounds of type 1, thus influencing positively the potency, selectivity and/or cytotoxicity of the new compounds.

-	~~==Function==~~	+	A new development of matrix metalloproteinase inhibitors: twin hydroxamic acids as potent inhibitors of MMPs.,Rossello A, Nuti E, Catalani MP, Carelli P, Orlandini E, Rapposelli S, Tuccinardi T, Atkinson SJ, Murphy G, Balsamo A Bioorg Med Chem Lett. 2005 May 2;15(9):2311-4. PMID:15837315<ref>PMID:15837315</ref>
-	~~[[http~~:~~//www~~.~~uniprot~~.~~org/uniprot/MMP9_HUMAN MMP9_HUMAN]]~~ May ~~play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly~~-~~\|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide~~.<ref>PMID:~~1480034~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4h82]] is~~ a ~~4 chain structure with 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=4H82 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	<references ~~group="xtra"~~/><~~references~~/>	+	*[[Matrix metalloproteinase\|Matrix metalloproteinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Gelatinase B]]		[[Category: Gelatinase B]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Antoni, C.]]		[[Category: Antoni, C.]]
	[[Category: Cassar-Lajeunesse, E.]]		[[Category: Cassar-Lajeunesse, E.]]

OCA at 07:50, 2 May 2013

OCA — Thu, 02 May 2013 07:50:33 GMT

←Older revision		Revision as of 07:50, 2 May 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4h82\| PDB=4h82 \| SCENE= }}
		+	===Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.===
		+	{{ABSTRACT_PUBMED_15837315}}

-	~~The~~ entry ~~4h82~~ is ~~ON HOLD until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] Defects in MMP9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:[http://omim.org/entry/603932 603932]]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.<ref>PMID:18455130</ref> Defects in MMP9 are the cause of metaphyseal anadysplasia type 2 (MANDP2) [MIM:[http://omim.org/entry/613073 613073]]. Metaphyseal anadysplasia consists of an abnormal bone development characterized by severe skeletal changes that, in contrast with the progressive course of most other skeletal dysplasias, resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.

-	~~Authors~~: ~~Antoni, C~~.~~, Stura, E~~.A.~~, Vera, L~~.~~, Cassar~~-~~Lajeunesse, E~~.~~, Nuti, E., Dive,~~ V.~~, Rossello, A~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-\|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref>

-	~~Description: Crystal~~ structure ~~of mutant MMP~~-~~9 catalytic domain in~~ complex ~~with a~~ twin inhibitor.	+	==About this Structure==
		+	[[4h82]] is a 4 chain structure with 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=4H82 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Gelatinase B]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Antoni, C.]]
		+	[[Category: Cassar-Lajeunesse, E.]]
		+	[[Category: Dive, V.]]
		+	[[Category: Nuti, E.]]
		+	[[Category: Rossello, A.]]
		+	[[Category: Stura, E A.]]
		+	[[Category: Vera, L.]]
		+	[[Category: Gelatinase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Hydrolase/twin inhibitor]]
		+	[[Category: Zincin-like]]

OCA at 06:57, 10 October 2012

OCA — Wed, 10 Oct 2012 06:57:05 GMT

←Older revision		Revision as of 06:57, 10 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4h82 is ON HOLD	+	The entry 4h82 is ON HOLD until Paper Publication

	Authors: Antoni, C., Stura, E.A., Vera, L., Cassar-Lajeunesse, E., Nuti, E., Dive, V., Rossello, A.		Authors: Antoni, C., Stura, E.A., Vera, L., Cassar-Lajeunesse, E., Nuti, E., Dive, V., Rossello, A.

	Description: Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.		Description: Crystal structure of mutant MMP-9 catalytic domain in complex with a twin inhibitor.