2ch2

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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16585514 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16585514}}
==About this Structure==
==About this Structure==
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[[Category: Plp-enzyme]]
[[Category: Plp-enzyme]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 09:52:18 2008''

Revision as of 06:52, 28 July 2008

Image:2ch2.png

Template:STRUCTURE 2ch2

STRUCTURE OF THE ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE IN COMPLEX WITH INHIBITOR

Template:ABSTRACT PUBMED 16585514

About this Structure

2CH2 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

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