PDBsum entry 4onc

Transferase

PDB id: 4onc

Contents

Protein chains

277 a.a.

Ligands

40B ×2

Waters ×437

PDB id:

4onc

Name:

Transferase

Title:

Crystal structure of mycobacterium tuberculosis decaprenyl diphosphate synthase in complex with bph-640

Structure:

Decaprenyl diphosphate synthase. Chain: a, b. Fragment: unp residues 13-296. Synonym: decapp, decaprenyl pyrophosphate synthase, long-chain isoprenyl diphosphate synthase, trans,polycis-decaprenyl diphosphate synthase. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: rv2361c. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.83Å R-factor: 0.159 R-free: 0.198

Authors:

X.Feng,H.C.Chan,T.P.Ko

Key ref:

H.C.Chan et al. (2014). Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from Mycobacterium tuberculosis. J Am Chem Soc, 136, 2892-2896. PubMed id: 24475925 DOI: 10.1021/ja413127v

Date:

28-Jan-14 Release date: 02-Apr-14

Protein chains

P9WFF7  (DPDS_MYCTU) -  Decaprenyl diphosphate synthase from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 296 a.a.

Struc: 277 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.5.1.86 - trans,polycis-decaprenyl diphosphate synthase.
• Reaction: (2Z,6E)-farnesyl diphosphate + 7 isopentenyl diphosphate = (2Z,6Z,10Z,14Z,18Z,22Z,26Z,30Z,34E)-decaprenyl diphosphate + 7 diphosphate
• Enzyme class 2: E.C.2.5.1.87 - ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl
• Reaction: n isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = a di-trans,poly-cis-polyprenyl diphosphate + n diphosphate

n isopentenyl diphosphate + 7 × (2E,6E)-farnesyl diphosphate = di-trans,poly-cis-polyprenyl diphosphate (Bound ligand (Het Group name = 40B) matches with 44.19% similarity) + n diphosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/ja413127v

J Am Chem Soc 136:2892-2896 (2014)

PubMed id: 24475925

Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from Mycobacterium tuberculosis.

H.C.Chan, X.Feng, T.P.Ko, C.H.Huang, Y.Hu, Y.Zheng, S.Bogue, C.Nakano, T.Hoshino, L.Zhang, P.Lv, W.Liu, D.C.Crick, P.H.Liang, A.H.Wang, E.Oldfield, R.T.Guo.

ABSTRACT

We have obtained the structure of the bacterial diterpene synthase, tuberculosinol/iso-tuberculosinol synthase (Rv3378c) from Mycobacterium tuberculosis , a target for anti-infective therapies that block virulence factor formation. This phosphatase adopts the same fold as found in the Z- or cis-prenyltransferases. We also obtained structures containing the tuberculosinyl diphosphate substrate together with one bisphosphonate inhibitor-bound structure. These structures together with the results of site-directed mutagenesis suggest an unusual mechanism of action involving two Tyr residues. Given the similarity in local and global structure between Rv3378c and the M. tuberculosis cis-decaprenyl diphosphate synthase (DPPS; Rv2361c), the possibility exists for the development of inhibitors that target not only virulence but also cell wall biosynthesis, based in part on the structures reported here.