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Crystal structure of Anopheles gambiae adenosine kinase in complex with P1,P4-di(adenosine-5) tetraphosphateCrystal structure of Anopheles gambiae adenosine kinase in complex with P1,P4-di(adenosine-5) tetraphosphate
Structural highlights
Publication Abstract from PubMedGenome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (Km 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with bound bisubstrate analogue Ap4A (2.0 A resolution) reveals interactions for adenosine, ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg2+ ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layered alpha/beta/alpha sandwich, and a small domain, termed the cap, in contact with adenosine. The specificity and tight-binding for adenosine arises from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168 and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64 and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. With 48% sequence identity, the overall structure is more similar to human adenosine kinase than to AK from Toxoplasma gondii (31% identity). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to its corresponding nucleotide suggesting an important role of this enzyme to maintain the adenosine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects. A High Affinity Adenosine Kinase from Anopheles gambiae.,Cassera MB, Ho MC, Merino EF, Burgos ES, Rinaldo-Matthis A, Almo SC, Schramm VL Biochemistry. 2011 Jan 19. PMID:21247194[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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