2ch1
From Proteopedia
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==Overview== | ==Overview== | ||
| - | In Anopheles gambiae, the vector for the most deadly malaria parasite | + | 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== | ==About this Structure== | ||
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[[Category: Arca, B.]] | [[Category: Arca, B.]] | ||
[[Category: Garavaglia, S.]] | [[Category: Garavaglia, S.]] | ||
| - | [[Category: Giovenzana, G | + | [[Category: Giovenzana, G B.]] |
[[Category: Li, J.]] | [[Category: Li, J.]] | ||
[[Category: Rizzi, M.]] | [[Category: Rizzi, M.]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:48:41 2008'' |
Revision as of 14:48, 21 February 2008
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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 with and as ligands. Known structural/functional Site: . 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 Thu Feb 21 16:48:41 2008
