3nx7: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-Hydroxy-2-(N-(2-hydroxyethyl)4-methoxyphenylsulfonamido)acetamide== | ==Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-Hydroxy-2-(N-(2-hydroxyethyl)4-methoxyphenylsulfonamido)acetamide== | ||
<StructureSection load='3nx7' size='340' side='right' caption='[[3nx7]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='3nx7' size='340' side='right'caption='[[3nx7]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3nx7]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3nx7]] is a 1 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=3NX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NX7 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=NHK:N-HYDROXY-N~2~-(2-HYDROXYETHYL)-N~2~-[(4-METHOXYPHENYL)SULFONYL]GLYCINAMIDE'>NHK</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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=NHK:N-HYDROXY-N~2~-(2-HYDROXYETHYL)-N~2~-[(4-METHOXYPHENYL)SULFONYL]GLYCINAMIDE'>NHK</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=3nx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nx7 OCA], [https://pdbe.org/3nx7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nx7 RCSB], [https://www.ebi.ac.uk/pdbsum/3nx7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nx7 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/MMP12_HUMAN 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. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nx/3nx7_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nx/3nx7_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 31: | Line 29: | ||
</div> | </div> | ||
<div class="pdbe-citations 3nx7" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3nx7" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bertini | [[Category: Bertini I]] | ||
[[Category: Calderone | [[Category: Calderone V]] | ||
[[Category: Fragai | [[Category: Fragai M]] | ||
[[Category: Giachetti | [[Category: Giachetti A]] | ||
[[Category: Loconte | [[Category: Loconte M]] | ||
[[Category: Luchinat | [[Category: Luchinat C]] | ||
[[Category: Maletta | [[Category: Maletta M]] | ||
[[Category: Nativi | [[Category: Nativi C]] | ||
[[Category: Yeo | [[Category: Yeo KJ]] | ||
Latest revision as of 12:23, 6 September 2023
Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-Hydroxy-2-(N-(2-hydroxyethyl)4-methoxyphenylsulfonamido)acetamideCrystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-Hydroxy-2-(N-(2-hydroxyethyl)4-methoxyphenylsulfonamido)acetamide
Structural highlights
FunctionMMP12_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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBy solving high-resolution crystal structures of a large number (14 in this case) of adducts of matrix metalloproteinase 12 (MMP12) with strong, nanomolar, inhibitors all derived from a single ligand scaffold, it is shown that the energetics of the ligand-protein interactions can be accounted for directly from the structures to a level of detail that allows us to rationalize for the differential binding affinity between pairs of closely related ligands. In each case, variations in binding affinities can be traced back to slight improvements or worsening of specific interactions with the protein of one or more ligand atoms. Isothermal calorimetry measurements show that the binding of this class of MMP inhibitors is largely enthalpy driven, but a favorable entropic contribution is always present. The binding enthalpy of acetohydroxamic acid (AHA), the prototype zinc-binding group in MMP drug discovery, has been also accurately measured. In principle, this research permits the planning of either improved inhibitors, or inhibitors with improved selectivity for one or another MMP. The present analysis is applicable to any drug target for which structural information on adducts with a series of homologous ligands can be obtained, while structural information obtained from in silico docking is probably not accurate enough for this type of study. Exploring the subtleties of drug-receptor interactions: the case of matrix metalloproteinases.,Bertini I, Calderone V, Fragai M, Giachetti A, Loconte M, Luchinat C, Maletta M, Nativi C, Yeo KJ J Am Chem Soc. 2007 Mar 7;129(9):2466-75. Epub 2007 Feb 2. PMID:17269766[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||