2hu6
From Proteopedia
(New page: 200px<br /> <applet load="2hu6" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hu6, resolution 1.32Å" /> '''Crystal structure o...) |
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| - | [[Image:2hu6. | + | [[Image:2hu6.jpg|left|200px]]<br /><applet load="2hu6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2hu6" size=" | + | |
caption="2hu6, resolution 1.32Å" /> | caption="2hu6, resolution 1.32Å" /> | ||
'''Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor'''<br /> | '''Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor'''<br /> | ||
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==Disease== | ==Disease== | ||
| - | Known diseases associated with this structure: Cardiomyopathy, dilated, 1G OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Cardiomyopathy, familial hypertrophic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Muscular dystrophy, limb-girdle, type 2J OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Myopathy, proximal, with early respiratory muscle involvement OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Tibial muscular dystrophy, tardive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]] | + | Known diseases associated with this structure: Cardiomyopathy, dilated, 1G OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Cardiomyopathy, familial hypertrophic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Muscular dystrophy, limb-girdle, type 2J OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Myopathy, early-onset, with fatal cardiomyopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Myopathy, proximal, with early respiratory muscle involvement OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]], Tibial muscular dystrophy, tardive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188840 188840]] |
==About this Structure== | ==About this Structure== | ||
| - | 2HU6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, CA, 37A and HAE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] Full crystallographic information is available from [http:// | + | 2HU6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=37A:'>37A</scene> and <scene name='pdbligand=HAE:'>HAE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HU6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: mmp-12]] | [[Category: mmp-12]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:33:43 2008'' |
Revision as of 15:33, 15 February 2008
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Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor
Contents |
Overview
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).
Disease
Known diseases associated with this structure: Cardiomyopathy, dilated, 1G OMIM:[188840], Cardiomyopathy, familial hypertrophic OMIM:[188840], Muscular dystrophy, limb-girdle, type 2J OMIM:[188840], Myopathy, early-onset, with fatal cardiomyopathy OMIM:[188840], Myopathy, proximal, with early respiratory muscle involvement OMIM:[188840], Tibial muscular dystrophy, tardive OMIM:[188840]
About this Structure
2HU6 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Macrophage elastase, with EC number 3.4.24.65 Full crystallographic information is available from OCA.
Reference
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
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