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2ch1
From Proteopedia
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[[Image:2ch1.gif|left|200px]] | [[Image:2ch1.gif|left|200px]] | ||
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'''STRUCTURE OF ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE''' | '''STRUCTURE OF ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE''' | ||
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[[Category: Rossi, F.]] | [[Category: Rossi, F.]] | ||
[[Category: 3-hydroxykynurenine transaminase]] | [[Category: 3-hydroxykynurenine transaminase]] | ||
| - | [[Category: | + | [[Category: Anopheles gambiae]] |
| - | [[Category: | + | [[Category: Kynurenine pathway]] |
| - | [[Category: | + | [[Category: Plp-enzyme]] |
| - | [[Category: | + | [[Category: Transferase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 22:07:18 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:07, 3 May 2008
STRUCTURE OF ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE
Overview
In Anopheles gambiae, the vector for the most deadly malaria parasite Plasmodium falciparum, xanthurenic acid (XA) plays a key role in parasite gametogenesis and fertility. In mosquitoes, XA is produced by transamination of 3-hydroxykynurenine (3-HK), a reaction that represents the main route to prevent the accumulation of the potentially toxic 3-HK excess. Interfering with XA metabolism in A. gambiae therefore appears an attractive avenue for the development of malaria transmission-blocking drugs and insecticides. We have determined the crystal structure of A. gambiae 3-HK transaminase in its pyridoxal 5'-phosphate form and in complex with a newly synthesized competitive enzyme inhibitor. Structural inspection of the enzyme active site reveals the key molecular determinants for ligand recognition and catalysis. Major contributions toward inhibitor binding are provided by a salt bridge between the inhibitor carboxylate and Arg-356 and by a remarkable hydrogen bond network involving the anthranilic moiety of the inhibitor and backbone atoms of residues Gly-25 and Asn-44. This study may be useful for the structure-based design of specific enzyme inhibitors of potential interest as antimalarial agents.
About this Structure
2CH1 is a Single protein structure of sequence from Anopheles gambiae. Full crystallographic information is available from OCA.
Reference
Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase., Rossi F, Garavaglia S, Giovenzana GB, Arca B, Li J, Rizzi M, Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5711-6. Epub 2006 Apr 3. PMID:16585514 Page seeded by OCA on Sat May 3 22:07:18 2008
