1dgf
From Proteopedia
(New page: 200px<br /> <applet load="1dgf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dgf, resolution 1.5Å" /> '''HUMAN ERYTHROCYTE CA...) |
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| - | [[Image:1dgf.gif|left|200px]]<br /> | + | [[Image:1dgf.gif|left|200px]]<br /><applet load="1dgf" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dgf" size=" | + | |
caption="1dgf, resolution 1.5Å" /> | caption="1dgf, resolution 1.5Å" /> | ||
'''HUMAN ERYTHROCYTE CATALASE'''<br /> | '''HUMAN ERYTHROCYTE CATALASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human catalase is an heme-containing peroxisomal enzyme that breaks down | + | Human catalase is an heme-containing peroxisomal enzyme that breaks down hydrogen peroxide to water and oxygen; it is implicated in ethanol metabolism, inflammation, apoptosis, aging and cancer. The 1. 5 A resolution human enzyme structure, both with and without bound NADPH, establishes the conserved features of mammalian catalase fold and assembly, implicates Tyr370 as the tyrosine radical, suggests the structural basis for redox-sensitive binding of cognate mRNA via the catalase NADPH binding site, and identifies an unexpectedly substantial number of water-mediated domain contacts. A molecular ruler mechanism based on observed water positions in the 25 A-long channel resolves problems for selecting hydrogen peroxide. Control of water-mediated hydrogen bonds by this ruler selects for the longer hydrogen peroxide and explains the paradoxical effects of mutations that increase active site access but lower catalytic rate. The heme active site is tuned without compromising peroxide binding through a Tyr-Arg-His-Asp charge relay, arginine residue to heme carboxylate group hydrogen bonding, and aromatic stacking. Structures of the non-specific cyanide and specific 3-amino-1,2, 4-triazole inhibitor complexes of human catalase identify their modes of inhibition and help reveal the catalytic mechanism of catalase. Taken together, these resting state and inhibited human catalase structures support specific, structure-based mechanisms for the catalase substrate recognition, reaction and inhibition and provide a molecular basis for understanding ethanol intoxication and the likely effects of human polymorphisms. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DGF 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 ACT, HEM and NDP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Catalase Catalase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.6 1.11.1.6] Full crystallographic information is available from [http:// | + | 1DGF 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=ACT:'>ACT</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=NDP:'>NDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Catalase Catalase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.6 1.11.1.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DGF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Arvai, A | + | [[Category: Arvai, A S.]] |
[[Category: Bourne, Y.]] | [[Category: Bourne, Y.]] | ||
| - | [[Category: Putnam, C | + | [[Category: Putnam, C D.]] |
| - | [[Category: Tainer, J | + | [[Category: Tainer, J A.]] |
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
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[[Category: nadph]] | [[Category: nadph]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:25 2008'' |
Revision as of 10:16, 21 February 2008
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HUMAN ERYTHROCYTE CATALASE
Contents |
Overview
Human catalase is an heme-containing peroxisomal enzyme that breaks down hydrogen peroxide to water and oxygen; it is implicated in ethanol metabolism, inflammation, apoptosis, aging and cancer. The 1. 5 A resolution human enzyme structure, both with and without bound NADPH, establishes the conserved features of mammalian catalase fold and assembly, implicates Tyr370 as the tyrosine radical, suggests the structural basis for redox-sensitive binding of cognate mRNA via the catalase NADPH binding site, and identifies an unexpectedly substantial number of water-mediated domain contacts. A molecular ruler mechanism based on observed water positions in the 25 A-long channel resolves problems for selecting hydrogen peroxide. Control of water-mediated hydrogen bonds by this ruler selects for the longer hydrogen peroxide and explains the paradoxical effects of mutations that increase active site access but lower catalytic rate. The heme active site is tuned without compromising peroxide binding through a Tyr-Arg-His-Asp charge relay, arginine residue to heme carboxylate group hydrogen bonding, and aromatic stacking. Structures of the non-specific cyanide and specific 3-amino-1,2, 4-triazole inhibitor complexes of human catalase identify their modes of inhibition and help reveal the catalytic mechanism of catalase. Taken together, these resting state and inhibited human catalase structures support specific, structure-based mechanisms for the catalase substrate recognition, reaction and inhibition and provide a molecular basis for understanding ethanol intoxication and the likely effects of human polymorphisms.
Disease
Known disease associated with this structure: Acatalasemia OMIM:[115500]
About this Structure
1DGF is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Catalase, with EC number 1.11.1.6 Full crystallographic information is available from OCA.
Reference
Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism., Putnam CD, Arvai AS, Bourne Y, Tainer JA, J Mol Biol. 2000 Feb 11;296(1):295-309. PMID:10656833
Page seeded by OCA on Thu Feb 21 12:16:25 2008
Categories: Catalase | Homo sapiens | Single protein | Arvai, A S. | Bourne, Y. | Putnam, C D. | Tainer, J A. | ACT | HEM | NDP | Heme | Hydrogen peroxide | Nadph
