1lwx
From Proteopedia
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. 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 Sat May 3 00:23:04 2008
