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2hu6

From Proteopedia

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{{Seed}}
 
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[[Image:2hu6.png|left|200px]]
 
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==Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor==
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The line below this paragraph, containing "STRUCTURE_2hu6", creates the "Structure Box" on the page.
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<StructureSection load='2hu6' size='340' side='right'caption='[[2hu6]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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</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>
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<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>
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{{STRUCTURE_2hu6| PDB=2hu6 | SCENE= }}
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<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>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hu/2hu6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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).
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===Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor===
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2hu6" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_16899369}}, adds the Publication Abstract to the page
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*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 16899369 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16899369}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2HU6 is a [[Single protein]] structure of 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].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/16899369 16899369]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Macrophage elastase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Calderone V]]
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[[Category: Calderone, V.]]
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[[Category: Fragai M]]
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[[Category: Fragai, M.]]
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[[Category: Guarna A]]
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[[Category: Guarna, A.]]
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[[Category: Machetti F]]
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[[Category: Machetti, F.]]
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[[Category: Mannino C]]
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[[Category: Mannino, C.]]
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[[Category: Nievo M]]
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[[Category: Nievo, M.]]
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[[Category: Papakyriakou A]]
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[[Category: Papakyriakou, A.]]
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[[Category: Drug design]]
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[[Category: Hydroxamic acid]]
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[[Category: Inhibitor]]
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[[Category: Macrophage metalloelastase]]
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[[Category: Matrix metalloproteinase]]
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[[Category: Mmp-12]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:45:33 2008''
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Current revision

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

PDB ID 2hu6

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