Substrate analogue complex structure of Mycobacterium tuberculosis decaprenyl diphosphate synthase
Tzu-Ping Ko, Xiansha Xiao, Rey-Ting Guo, Jian-Wen Huang, Weidong Liu, Chun-Chi Chen [1]
Molecular Tour
Rv1086 produces ־©-E,Z-farnesyl diphosphate (EZ-FPP, C15) from geranyl diphosphate (GPP, C10) and isopentenyl diphosphate (IPP, C5) that is used by Rv2361c for further elongation to form decaprenyl diphosphate (DPP, C50). In this structure we have substrate analogues of GPP and IPP as well as the essential Mg ion bound to Rv2361 (i.e. MtDPPS) in a productive mode. GPP binds to S1 site and IPP binds to S2 site. The hydrocarbon chains are joined head-to-tail to form a 5-carbon longer product. Meanwhile, we also have the GPP analogue bound in alternate conformations. The varying interactions of this substrate with Asp76 from one subunit and Arg292 from another may account for the transition pathway from S2 site to S1 site after each cycle of elongation reaction. So the enzyme can proceed to the next cycle of catalysis.
References
- ↑ Ko TP, Xiao X, Guo RT, Huang JW, Liu W, Chen CC. Substrate-analogue complex structure of Mycobacterium tuberculosis decaprenyl diphosphate synthase. Acta Crystallogr F Struct Biol Commun. 2019 Apr 1;75(Pt 4):212-216. PMID:30950820 doi:10.1107/S2053230X19001213
