2dy5
From Proteopedia
(New page: 200px<br /><applet load="2dy5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dy5, resolution 2.70Å" /> '''Crystal structure of...) |
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| - | [[Image:2dy5.jpg|left|200px]]<br /><applet load="2dy5" size=" | + | [[Image:2dy5.jpg|left|200px]]<br /><applet load="2dy5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2dy5, resolution 2.70Å" /> | caption="2dy5, resolution 2.70Å" /> | ||
'''Crystal structure of rat heme oxygenase-1 in complex with heme and 2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane'''<br /> | '''Crystal structure of rat heme oxygenase-1 in complex with heme and 2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2DY5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CL, HEM and 224 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] Full crystallographic information is available from [http:// | + | 2DY5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=224:'>224</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DY5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: substrate bound structure]] | [[Category: substrate bound structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:10:43 2008'' |
Revision as of 13:10, 23 January 2008
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Crystal structure of rat heme oxygenase-1 in complex with heme and 2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
Overview
Heme oxygenase (HO) catalyzes the regiospecific cleavage of the porphyrin, ring of heme using reducing equivalents and O2 to produce biliverdin, iron, and CO. Because CO has a cytoprotective effect through the p38-MAPK, pathway, HO is a potential therapeutic target in cancer. In fact, inhibition of the HO isoform HO-1 reduces Kaposi sarcoma tumor growth., Imidazole-dioxolane compounds have recently attracted attention because, they have been reported to specifically inhibit HO-1, but not HO-2, unlike, Cr-containing protoporphyrin IX, a classical inhibitor of HO, that, inhibits not only both HO isoforms but also other hemoproteins. The, inhibitory mechanism of imidazole-dioxolane compounds, however, has not, yet been characterized. Here, we determine the crystal structure of the, ternary complex of rat HO-1, heme, and an imidazole-dioxolane compound, 2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane., This compound bound on the distal side of the heme iron, where the, imidazole and 4-chlorophenyl groups were bound to the heme iron and the, hydrophobic cavity in HO, respectively. Binding of the bulky inhibitor in, the narrow distal pocket shifted the distal helix to open the distal site, and moved both the heme and the proximal helix. Furthermore, the, biochemical characterization revealed that the catalytic reactions of both, HO-1 and HO-2 were completely stopped after the formation of verdoheme in, the presence of the imidazole-dioxolane compound. This result should be, mainly due to the lower reactivity of the inhibitor-bound verdoheme with, O2 compared to the reactivity of the inhibitor-bound heme with O2.
About this Structure
2DY5 is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Active as Heme oxygenase, with EC number 1.14.99.3 Full crystallographic information is available from OCA.
Reference
X-ray crystallographic and biochemical characterization of the inhibitory action of an imidazole-dioxolane compound on heme oxygenase., Sugishima M, Higashimoto Y, Oishi T, Takahashi H, Sakamoto H, Noguchi M, Fukuyama K, Biochemistry. 2007 Feb 20;46(7):1860-7. Epub 2007 Jan 25. PMID:17253780
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