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[[ | ==Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(4-methoxy-N(2-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)ethyl)phenylsulfonamido)acetamide== | ||
<StructureSection load='3n2u' size='340' side='right' caption='[[3n2u]], [[Resolution|resolution]] 1.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3n2u]] is a 1 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=3N2U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N2U 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=D3X:N-HYDROXY-2-{[(4-METHOXYPHENYL)SULFONYL](2-{[(2R,3R,4S,5S,6R)-3,4,5-TRIHYDROXY-6-(HYDROXYMETHYL)TETRAHYDRO-2H-PYRAN-2-YL]OXY}ETHYL)AMINO}ACETAMIDE'>D3X</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">[[3f15|3f15]], [[3f16|3f16]], [[3f17|3f17]], [[3n2v|3n2v]]</td></tr> | |||
<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 Homo sapiens])</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=3n2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n2u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n2u RCSB], [http://www.ebi.ac.uk/pdbsum/3n2u PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
N-Arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water. | |||
Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).,Attolino E, Calderone V, Dragoni E, Fragai M, Richichi B, Luchinat C, Nativi C Eur J Med Chem. 2010 Oct 19. PMID:20965620<ref>PMID:20965620</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Matrix metalloproteinase|Matrix metalloproteinase]] | *[[Matrix metalloproteinase|Matrix metalloproteinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Macrophage elastase]] | [[Category: Macrophage elastase]] | ||
[[Category: Calderone, V | [[Category: Calderone, V]] | ||
[[Category: Elastase]] | [[Category: Elastase]] | ||
[[Category: Extracellular matrix]] | [[Category: Extracellular matrix]] | ||
Revision as of 12:52, 9 December 2014
Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(4-methoxy-N(2-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)ethyl)phenylsulfonamido)acetamideCrystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(4-methoxy-N(2-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)ethyl)phenylsulfonamido)acetamide
Structural highlights
Publication Abstract from PubMedN-Arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water. Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).,Attolino E, Calderone V, Dragoni E, Fragai M, Richichi B, Luchinat C, Nativi C Eur J Med Chem. 2010 Oct 19. PMID:20965620[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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