1d5j

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:49, 7 February 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1d5j.gif|left|200px]]
 
-
{{Structure
+
==CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR.==
-
|PDB= 1d5j |SIZE=350|CAPTION= <scene name='initialview01'>1d5j</scene>, resolution 2.6&Aring;
+
<StructureSection load='1d5j' size='340' side='right'caption='[[1d5j]], [[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=MM3:N-HYDROXY-4-[(4-METHOXYLPHENYL)SULFONYL]-2,2-DIMETHYL-HEXAHYDRO-1,4-THIAZEPINE-3(S)-CARBOXAMIDE'>MM3</scene>
+
<table><tr><td colspan='2'>[[1d5j]] 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=1D5J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D5J FirstGlance]. <br>
-
|ACTIVITY= [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]
+
</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=MM3:N-HYDROXY-4-[(4-METHOXYLPHENYL)SULFONYL]-2,2-DIMETHYL-HEXAHYDRO-1,4-THIAZEPINE-3(S)-CARBOXAMIDE'>MM3</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=1d5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d5j OCA], [https://pdbe.org/1d5j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d5j RCSB], [https://www.ebi.ac.uk/pdbsum/1d5j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d5j ProSAT]</span></td></tr>
 +
</table>
 +
== 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/d5/1d5j_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=1d5j ConSurf].
 +
<div style="clear:both"></div>
-
'''CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR.'''
+
==See Also==
-
 
+
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
-
 
+
== References ==
-
==Overview==
+
<references/>
-
The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC(50)'s against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.
+
__TOC__
-
 
+
</StructureSection>
-
==Disease==
+
[[Category: Homo sapiens]]
-
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=185250 185250]]
+
[[Category: Large Structures]]
-
 
+
[[Category: Almstead NG]]
-
==About this Structure==
+
[[Category: Bradley RS]]
-
1D5J is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D5J OCA].
+
[[Category: De B]]
-
 
+
[[Category: Natchus MG]]
-
==Reference==
+
[[Category: Pikul S]]
-
Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors., Almstead NG, Bradley RS, Pikul S, De B, Natchus MG, Taiwo YO, Gu F, Williams LE, Hynd BA, Janusz MJ, Dunaway CM, Mieling GE, J Med Chem. 1999 Nov 4;42(22):4547-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10579818 10579818]
+
-
[[Category: Single protein]]
+
-
[[Category: Stromelysin 1]]
+
-
[[Category: Almstead, N G.]]
+
-
[[Category: Bradley, R S.]]
+
-
[[Category: De, B.]]
+
-
[[Category: Natchus, M G.]]
+
-
[[Category: Pikul, S.]]
+
-
[[Category: CA]]
+
-
[[Category: MM3]]
+
-
[[Category: ZN]]
+
-
[[Category: inhibited]]
+
-
[[Category: mixed alpha beta structure]]
+
-
[[Category: zinc protease]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:33:06 2008''
+

Current revision

CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A THIAZEPINE BASED INHIBITOR.

PDB ID 1d5j

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1d5j"
Personal tools