1lwx
From Proteopedia
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AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE
Overview
To be effective as antiviral agent, AZT (3'-azido-3'-deoxythymidine) must, be converted to a triphosphate derivative by cellular kinases. The, conversion is inefficient and, to understand why AZT diphosphate is a poor, substrate of nucleoside diphosphate (NDP) kinase, we determined a 2.3-A, x-ray structure of a complex with the N119A point mutant of Dictyostelium, NDP kinase. It shows that the analog binds at the same site and, except, for the sugar ring pucker which is different, binds in the same way as the, natural substrate thymidine diphosphate. However, the azido group that, replaces the 3'OH of the deoxyribose in AZT displaces a lysine side chain, involved in catalysis. Moreover, it is unable to make an internal hydrogen, bond to the oxygen bridging the beta- and gamma-phosphate, which plays an, important part in phosphate transfer.
About this Structure
1LWX is a Single protein structure of sequence from Dictyostelium discoideum with MG and AZD as ligands. Active as Nucleoside-diphosphate kinase, with EC number 2.7.4.6 Full crystallographic information is available from OCA.
Reference
X-ray analysis of azido-thymidine diphosphate binding to nucleoside diphosphate kinase., Xu Y, Sellam O, Morera S, Sarfati S, Biondi R, Veron M, Janin J, Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7162-5. PMID:9207061
Page seeded by OCA on Tue Nov 20 20:57:14 2007
