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| {{STRUCTURE_2ch2| PDB=2ch2 | SCENE= }} | | {{STRUCTURE_2ch2| PDB=2ch2 | SCENE= }} |
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| '''STRUCTURE OF THE ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE IN COMPLEX WITH INHIBITOR'''
| | ===STRUCTURE OF THE ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE IN COMPLEX WITH INHIBITOR=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16585514}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16585514 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16585514}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Plp-enzyme]] | | [[Category: Plp-enzyme]] |
| [[Category: Transferase]] | | [[Category: Transferase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 22:07:41 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 09:52:18 2008'' |
