3rts: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Human MMP-12 catalytic domain in complex with*N*-Hydroxy-2-(2-phenylethylsulfonamido)acetamide== | ==Human MMP-12 catalytic domain in complex with*N*-Hydroxy-2-(2-phenylethylsulfonamido)acetamide== | ||
<StructureSection load='3rts' size='340' side='right' caption='[[3rts]], [[Resolution|resolution]] 1.81Å' scene=''> | <StructureSection load='3rts' size='340' side='right'caption='[[3rts]], [[Resolution|resolution]] 1.81Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3rts]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3rts]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RTS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RTS 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=KLG:N-HYDROXY-N~2~-[(2-PHENYLETHYL)SULFONYL]GLYCINAMIDE'>KLG</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=KLG:N-HYDROXY-N~2~-[(2-PHENYLETHYL)SULFONYL]GLYCINAMIDE'>KLG</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">[[3lk8|3lk8]], [[3nx7|3nx7]], [[3f15|3f15]], [[3f16|3f16]], [[3f17|3f17]], [[3f1a|3f1a]], [[3rtt|3rtt]], [[3rtu|3rtu]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3lk8|3lk8]], [[3nx7|3nx7]], [[3f15|3f15]], [[3f16|3f16]], [[3f17|3f17]], [[3f1a|3f1a]], [[3rtt|3rtt]], [[3rtu|3rtu]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([https://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'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rts OCA], [https://pdbe.org/3rts PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rts RCSB], [https://www.ebi.ac.uk/pdbsum/3rts PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rts ProSAT]</span></td></tr> | ||
</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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 21: | ||
</div> | </div> | ||
<div class="pdbe-citations 3rts" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3rts" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 26: | Line 29: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Macrophage elastase]] | [[Category: Macrophage elastase]] | ||
[[Category: Bertini, I]] | [[Category: Bertini, I]] | ||
Revision as of 13:24, 22 June 2022
Human MMP-12 catalytic domain in complex with*N*-Hydroxy-2-(2-phenylethylsulfonamido)acetamideHuman MMP-12 catalytic domain in complex with*N*-Hydroxy-2-(2-phenylethylsulfonamido)acetamide
Structural highlights
Function[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. 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
|
| ||||||||||||||||||||||