2hu6

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "2hu6" [edit=sysop:move=sysop])
Current revision (10:01, 30 August 2023) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2hu6.png|left|200px]]
 
-
<!--
+
==Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor==
-
The line below this paragraph, containing "STRUCTURE_2hu6", creates the "Structure Box" on the page.
+
<StructureSection load='2hu6' size='340' side='right'caption='[[2hu6]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[2hu6]] 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=2HU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HU6 FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.32&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=37A:(1S,5S,7R)-N~7~-(BIPHENYL-4-YLMETHYL)-N~3~-HYDROXY-6,8-DIOXA-3-AZABICYCLO[3.2.1]OCTANE-3,7-DICARBOXAMIDE'>37A</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-
{{STRUCTURE_2hu6| PDB=2hu6 | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hu6 OCA], [https://pdbe.org/2hu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hu6 RCSB], [https://www.ebi.ac.uk/pdbsum/2hu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hu6 ProSAT]</span></td></tr>
 +
</table>
 +
== 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 ==
 +
[[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/hu/2hu6_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=2hu6 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Starting from 3-aza-6,8-dioxa-bicyclo[3.2.1]octane scaffold (BTAa) a virtual library of molecules was generated and screened in silico against the crystal structure of the Human Macrophage Metalloelastase (MMP-12). The molecules obtaining high score were synthesized and the affinity for the catalytic domain of MMP-12 was experimentally proved by NMR experiments. A BTAa scaffold 20 having a N-hydroxyurea group in position 3 and a p-phenylbenzylcarboxy amide in position 7 showed a fair inhibition potency (IC50 = 149 microM) for MMP-12 and some selectivity towards five different MMPs. These results, taken together with the X-ray structure of the adduct between MMP-12, the inhibitor 20 and the acetohydroxamic acid (AHA), suggest that bicyclic scaffold derivatives may be exploited for the design of new selective matrix metalloproteinase inhibitors (MMPIs).
-
===Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor===
+
Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors.,Mannino C, Nievo M, Machetti F, Papakyriakou A, Calderone V, Fragai M, Guarna A Bioorg Med Chem. 2006 Nov 15;14(22):7392-403. Epub 2006 Aug 8. PMID:16899369<ref>PMID:16899369</ref>
-
 
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
<!--
+
</div>
-
The line below this paragraph, {{ABSTRACT_PUBMED_16899369}}, adds the Publication Abstract to the page
+
<div class="pdbe-citations 2hu6" style="background-color:#fffaf0;"></div>
-
(as it appears on PubMed at http://www.pubmed.gov), where 16899369 is the PubMed ID number.
+
-
-->
+
-
{{ABSTRACT_PUBMED_16899369}}
+
-
 
+
-
==About this Structure==
+
-
[[2hu6]] is a 1 chain structure of [[Elastase]] 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=2HU6 OCA].
+
==See Also==
==See Also==
-
*[[Elastase]]
+
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:16899369</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Macrophage elastase]]
+
[[Category: Large Structures]]
-
[[Category: Calderone, V.]]
+
[[Category: Calderone V]]
-
[[Category: Fragai, M.]]
+
[[Category: Fragai M]]
-
[[Category: Guarna, A.]]
+
[[Category: Guarna A]]
-
[[Category: Machetti, F.]]
+
[[Category: Machetti F]]
-
[[Category: Mannino, C.]]
+
[[Category: Mannino C]]
-
[[Category: Nievo, M.]]
+
[[Category: Nievo M]]
-
[[Category: Papakyriakou, A.]]
+
[[Category: Papakyriakou A]]
-
[[Category: Drug design]]
+
-
[[Category: Hydrolase]]
+
-
[[Category: Hydroxamic acid]]
+
-
[[Category: Inhibitor]]
+
-
[[Category: Macrophage metalloelastase]]
+
-
[[Category: Matrix metalloproteinase]]
+
-
[[Category: Mmp-12]]
+

Current revision

Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor

PDB ID 2hu6

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/2hu6"
Personal tools