1LWX

AZT DIPHOSPHATE BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE

Summary for 1LWX

• Entry DOI: 10.2210/pdb1lwx/pdb
• Descriptor: NUCLEOSIDE DIPHOSPHATE KINASE, MAGNESIUM ION, 3'-AZIDO-3'-DEOXYTHYMIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: phosphotransferase, antiviral agent, azidothymidine
• Biological source: Dictyostelium discoideum
• Cellular location: Cytoplasm: P22887
• Total number of polymer chains: 3
• Total formula weight: 51650.15

Authors

Janin, J.,Xu, Y. (deposition date: 1997-04-30, release date: 1997-08-20, Last modification date: 2024-02-14)

Primary citation

Xu, Y.,Sellam, O.,Morera, S.,Sarfati, S.,Biondi, R.,Veron, M.,Janin, J.
X-ray analysis of azido-thymidine diphosphate binding to nucleoside diphosphate kinase.
Proc.Natl.Acad.Sci.USA, 94:7162-7165, 1997

PubMed Abstract: 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.

PubMed: 9207061
DOI: 10.1073/pnas.94.14.7162

Experimental method

X-RAY DIFFRACTION (2.3 Å)