2std
From Proteopedia
(New page: 200px<br /><applet load="2std" size="450" color="white" frame="true" align="right" spinBox="true" caption="2std, resolution 2.1Å" /> '''SCYTALONE DEHYDRATASE...) |
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| - | [[Image:2std.gif|left|200px]]<br /><applet load="2std" size=" | + | [[Image:2std.gif|left|200px]]<br /><applet load="2std" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2std, resolution 2.1Å" /> | caption="2std, resolution 2.1Å" /> | ||
'''SCYTALONE DEHYDRATASE COMPLEXED WITH TIGHT-BINDING INHIBITOR CARPROPAMID'''<br /> | '''SCYTALONE DEHYDRATASE COMPLEXED WITH TIGHT-BINDING INHIBITOR CARPROPAMID'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Scytalone dehydratase is a member of the group of enzymes involved in | + | Scytalone dehydratase is a member of the group of enzymes involved in fungal melanin biosynthesis in a phytopathogenic fungus, Pyricularia oryzae, which causes rice blast disease. Carpropamid [(1RS,3SR)-2, 2-dichloro-N-[(R)-1-(4-chlorophenyl)ethyl]-1-ethyl-3-methylcyclopropa necarboxamide] is a tight-binding inhibitor of the enzyme. To clarify the structural basis for tight-binding inhibition, the crystal structure of the enzyme complexed with carpropamid was analyzed using diffraction data collected at 100 K. The structural model was refined to a crystallographic R-factor of 0.180 against reflections up to a resolution of 2.1 A. Carpropamid was bound in a hydrophobic cavity of the enzyme. Three types of interactions appeared to contribute to the binding. (i) A hydrogen bond was formed between a chloride atom in the dichloromethylethylcyclopropane ring of carpropamid and Asn-131 of the enzyme. (ii) The (chlorophenyl)ethyl group of carpropamid built strong contacts with Val-75, and this group further formed a cluster of aromatic rings together with four aromatic residues in the enzyme (Tyr-50, Phe-53, Phe-158, and Phe-162). (iii) Two hydration water molecules bound to the carboxamide group of carpropamid, and they were further hydrogen-bonded to Tyr-30, Tyr-50, His-85, and His-110. As a result of interactions between carpropamid and the phenylalanine residues (Phe-158 and Phe-162) in the C-terminal region of the enzyme, the C-terminal region completely covered the inhibitor, ensuring its localization in the cavity. |
==About this Structure== | ==About this Structure== | ||
| - | 2STD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Magnaporthe_grisea Magnaporthe grisea] with SO4 and CRP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Scytalone_dehydratase Scytalone dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.94 4.2.1.94] Full crystallographic information is available from [http:// | + | 2STD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Magnaporthe_grisea Magnaporthe grisea] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=CRP:'>CRP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Scytalone_dehydratase Scytalone dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.94 4.2.1.94] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2STD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: melanine biosynthesis]] | [[Category: melanine biosynthesis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:49:31 2008'' |
Revision as of 16:49, 21 February 2008
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SCYTALONE DEHYDRATASE COMPLEXED WITH TIGHT-BINDING INHIBITOR CARPROPAMID
Overview
Scytalone dehydratase is a member of the group of enzymes involved in fungal melanin biosynthesis in a phytopathogenic fungus, Pyricularia oryzae, which causes rice blast disease. Carpropamid [(1RS,3SR)-2, 2-dichloro-N-[(R)-1-(4-chlorophenyl)ethyl]-1-ethyl-3-methylcyclopropa necarboxamide] is a tight-binding inhibitor of the enzyme. To clarify the structural basis for tight-binding inhibition, the crystal structure of the enzyme complexed with carpropamid was analyzed using diffraction data collected at 100 K. The structural model was refined to a crystallographic R-factor of 0.180 against reflections up to a resolution of 2.1 A. Carpropamid was bound in a hydrophobic cavity of the enzyme. Three types of interactions appeared to contribute to the binding. (i) A hydrogen bond was formed between a chloride atom in the dichloromethylethylcyclopropane ring of carpropamid and Asn-131 of the enzyme. (ii) The (chlorophenyl)ethyl group of carpropamid built strong contacts with Val-75, and this group further formed a cluster of aromatic rings together with four aromatic residues in the enzyme (Tyr-50, Phe-53, Phe-158, and Phe-162). (iii) Two hydration water molecules bound to the carboxamide group of carpropamid, and they were further hydrogen-bonded to Tyr-30, Tyr-50, His-85, and His-110. As a result of interactions between carpropamid and the phenylalanine residues (Phe-158 and Phe-162) in the C-terminal region of the enzyme, the C-terminal region completely covered the inhibitor, ensuring its localization in the cavity.
About this Structure
2STD is a Single protein structure of sequence from Magnaporthe grisea with and as ligands. Active as Scytalone dehydratase, with EC number 4.2.1.94 Full crystallographic information is available from OCA.
Reference
Cryogenic X-ray crystal structure analysis for the complex of scytalone dehydratase of a rice blast fungus and its tight-binding inhibitor, carpropamid: the structural basis of tight-binding inhibition., Nakasako M, Motoyama T, Kurahashi Y, Yamaguchi I, Biochemistry. 1998 Jul 14;37(28):9931-9. PMID:9665698
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