6IME

Rv2361c complex with substrate analogues

Summary for 6IME

• Entry DOI: 10.2210/pdb6ime/pdb
• Related: 4onc
• Descriptor: Decaprenyl diphosphate synthase, GERANYL S-THIOLODIPHOSPHATE, MAGNESIUM ION, ... (9 entities in total)
• Functional Keywords: decaprenyl diphosphate synthesis, substrate binding mode, catalytic mechanism, rossmann-like fold, butterfly, transferase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 68991.85

Authors

Ko, T.-P.,Guo, R.-T.,Chen, C.-C.,Liu, W. (deposition date: 2018-10-22, release date: 2019-09-04, Last modification date: 2023-11-22)

Primary citation

Ko, T.-P.,Xiao, X.,Guo, R.-T.,Huang, J.-W.,Liu, W.,Chen, C.-C.
Substrate-analogue complex structure of Mycobacterium tuberculosis decaprenyl diphosphate synthase.
Acta Crystallogr.,Sect.F, 75:212-216, 2019

PubMed Abstract: Decaprenyl diphosphate synthase from Mycobacterium tuberculosis (MtDPPS, also known as Rv2361c) catalyzes the consecutive elongation of ω,E,Z-farnesyl diphosphate (EZ-FPP) by seven isoprene units by forming new cis double bonds. The protein folds into a butterfly-like homodimer like most other cis-type prenyltransferases. The starting allylic substrate EZ-FPP is bound to the S1 site and the homoallylic substrate to be incorporated, isopentenyl diphosphate, is bound to the S2 site. Here, a 1.55 Å resolution structure of MtDPPS in complex with the substrate analogues geranyl S-thiodiphosphate (GSPP) and isopentenyl S-thiodiphosphate bound to their respective sites in one subunit clearly shows the active-site configuration and the magnesium-coordinated geometry for catalysis. The ligand-binding mode of GSPP in the other subunit indicates a possible pathway of product translocation from the S2 site to the S1 site, as required for the next step of the reaction. The preferred binding of negatively charged effectors to the S1 site also suggests a promising direction for inhibitor design.

PubMed: 30950820
DOI: 10.1107/S2053230X19001213

Experimental method

X-RAY DIFFRACTION (1.55 Å)