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[[Image:1biw.jpg|left|200px]]


{{Structure
==DESIGN AND SYNTHESIS OF CONFORMATIONALLY-CONSTRAINED MMP INHIBITORS==
|PDB= 1biw |SIZE=350|CAPTION= <scene name='initialview01'>1biw</scene>, resolution 2.5&Aring;
<StructureSection load='1biw' size='340' side='right'caption='[[1biw]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=S80:N1-HYDROXY-2-(3-HYDROXY-PROPYL)-3-ISOBUTYL-N4-[1-(2-METHOXY-ETHYL)-2-OXO-AZEPAN-3-YL]-SUCCINAMIDE'>S80</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
<table><tr><td colspan='2'>[[1biw]] 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=1BIW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BIW FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#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=S80:N1-HYDROXY-2-(3-HYDROXY-PROPYL)-3-ISOBUTYL-N4-[1-(2-METHOXY-ETHYL)-2-OXO-AZEPAN-3-YL]-SUCCINAMIDE'>S80</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1biw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1biw OCA], [https://pdbe.org/1biw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1biw RCSB], [https://www.ebi.ac.uk/pdbsum/1biw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1biw ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1biw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1biw OCA], [http://www.ebi.ac.uk/pdbsum/1biw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1biw RCSB]</span>
== Disease ==
}}
[https://www.uniprot.org/uniprot/MMP3_HUMAN MMP3_HUMAN] Defects in MMP3 are the cause of susceptibility to coronary heart disease type 6 (CHDS6) [MIM:[https://omim.org/entry/614466 614466]. A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. Note=A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.<ref>PMID:8662692</ref> <ref>PMID:12477941</ref>
== Function ==
[https://www.uniprot.org/uniprot/MMP3_HUMAN MMP3_HUMAN] Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.
== 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/bi/1biw_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=1biw ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel series of conformationally constrained matrix metalloprotease inhibitors was identified. The potencies observed for these inhibitors were highly dependent upon the substitution pattern on the caprolactam ring as well as the succinate moiety.


'''DESIGN AND SYNTHESIS OF CONFORMATIONALLY-CONSTRAINED MMP INHIBITORS'''
Design and synthesis of conformationally-constrained MMP inhibitors.,Natchus MG, Cheng M, Wahl CT, Pikul S, Almstead NG, Bradley RS, Taiwo YO, Mieling GE, Dunaway CM, Snider CE, McIver JM, Barnett BL, McPhail SJ, Anastasio MB, De B Bioorg Med Chem Lett. 1998 Aug 18;8(16):2077-80. PMID:9873489<ref>PMID:9873489</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1biw" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
A novel series of conformationally constrained matrix metalloprotease inhibitors was identified. The potencies observed for these inhibitors were highly dependent upon the substitution pattern on the caprolactam ring as well as the succinate moiety.
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1BIW 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=1BIW OCA].
__TOC__
 
</StructureSection>
==Reference==
Design and synthesis of conformationally-constrained MMP inhibitors., Natchus MG, Cheng M, Wahl CT, Pikul S, Almstead NG, Bradley RS, Taiwo YO, Mieling GE, Dunaway CM, Snider CE, McIver JM, Barnett BL, McPhail SJ, Anastasio MB, De B, Bioorg Med Chem Lett. 1998 Aug 18;8(16):2077-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9873489 9873489]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Stromelysin 1]]
[[Category: Almstead NG]]
[[Category: Almstead, N G.]]
[[Category: Anastasio MB]]
[[Category: Anastasio, M B.]]
[[Category: Barnett BL]]
[[Category: Barnett, B L.]]
[[Category: Bradley RS]]
[[Category: Bradley, R S.]]
[[Category: Cheng M]]
[[Category: Cheng, M.]]
[[Category: De B]]
[[Category: De, B.]]
[[Category: Dunaway CM]]
[[Category: Dunaway, C M.]]
[[Category: McIver JM]]
[[Category: McIver, J M.]]
[[Category: McPhail SJ]]
[[Category: McPhail, S J.]]
[[Category: Mieling GE]]
[[Category: Mieling, G E.]]
[[Category: Natchus MG]]
[[Category: Natchus, M G.]]
[[Category: Pikul S]]
[[Category: Pikul, S.]]
[[Category: Snider CE]]
[[Category: Snider, C E.]]
[[Category: Taiwo YO]]
[[Category: Taiwo, Y O.]]
[[Category: Wahl CT]]
[[Category: Wahl, C T.]]
[[Category: matrix metalloprotease]]
[[Category: osteoarthritis]]
[[Category: protein crystal structure]]
[[Category: stromelysin]]
[[Category: structure-based drug design]]
 
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