1a86: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(6 intermediate revisions by the same user not shown)
Line 1: Line 1:
==MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR==
==MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR==
<StructureSection load='1a86' size='340' side='right' caption='[[1a86]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='1a86' size='340' side='right'caption='[[1a86]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1a86]] 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=1A86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1A86 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1a86]] 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=1A86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A86 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0ZB:N-BENZYL-N~2~-[(2R)-2-(HYDROXYCARBAMOYL)-4-METHYLPENTANOYL]-L-ALPHA-ASPARAGINE'>0ZB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</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&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Neutrophil_collagenase Neutrophil collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.34 3.4.24.34] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ZB:N-BENZYL-N~2~-[(2R)-2-(HYDROXYCARBAMOYL)-4-METHYLPENTANOYL]-L-ALPHA-ASPARAGINE'>0ZB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1a86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1a86 RCSB], [http://www.ebi.ac.uk/pdbsum/1a86 PDBsum]</span></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=1a86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a86 OCA], [https://pdbe.org/1a86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a86 RCSB], [https://www.ebi.ac.uk/pdbsum/1a86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a86 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MMP8_HUMAN MMP8_HUMAN] Can degrade fibrillar type I, II, and III collagens.
== 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/a8/1a86_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a8/1a86_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>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=1a86 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases, which have been implicated in various disease processes. Various classes of MMP inhibitors, including hydroxamic acids, phosphinic acids, and thiols, have been previously described. Most of these mimic peptides, and most likely bind analogous to the corresponding peptide substrates. Among the hydroxamic acids, malonic acid derivatives have been used as MMP inhibitors, although optimization of their inhibition potency was not successful. Here we report the design of malonic acid-based inhibitors using the X-ray structure of a collagenase/inhibitor complex, which revealed a nonsubstrate-like binding mode. The proposed beta-type turn-like conformation for the improved inhibitors was confirmed by X-ray crystallography. The observation of nonsubstrate-like binding confirms the original strategy for structure-based modeling of improved malonic acid inhibitors, and explains kinetic data that are inconsistent with substrate-like binding. Detailed interactions for the improved inhibitors seen in the crystal structure also suggest possibilities for further modifications in cycles of structure based drug design. Indeed, we have designed nonpeptidic inhibitors with approximately 500-fold improved inhibition based on these structures.
Structure of malonic acid-based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data.,Brandstetter H, Engh RA, Von Roedern EG, Moroder L, Huber R, Bode W, Grams F Protein Sci. 1998 Jun;7(6):1303-9. PMID:9655333<ref>PMID:9655333</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Matrix metalloproteinase|Matrix metalloproteinase]]
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Neutrophil collagenase]]
[[Category: Large Structures]]
[[Category: Brandstetter, H]]
[[Category: Brandstetter H]]
[[Category: Engh, R A]]
[[Category: Engh RA]]
[[Category: Grams, F]]
[[Category: Grams F]]
[[Category: Roedern, E G.V]]
[[Category: Roedern EGV]]
[[Category: Collagenase]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Malonic acid]]
[[Category: Matrix metalloproteinase]]
[[Category: Mmp8]]

Latest revision as of 09:28, 7 February 2024

MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITORMMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR

Structural highlights

1a86 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MMP8_HUMAN Can degrade fibrillar type I, II, and III collagens.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1a86, resolution 2.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1a86&oldid=4039964"