PDBsum entry 1u3p

Lyase

PDB id: 1u3p

Contents

Protein chain

155 a.a. *

Metals

_ZN

Waters ×1

* Residue conservation analysis

PDB id:

1u3p

Name:

Lyase

Title:

Ispf native

Structure:

2-c-methyl-d-erythritol 2,4-cyclodiphosphate synthase. Chain: a. Synonym: mecps, mecdp-synthase, ispf. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: ispf, mecs. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Trimer (from PDB file)

Resolution:

2.85Å R-factor: 0.226 R-free: 0.237

Authors:

S.Steinbacher,J.Kaiser,J.Wungsintaweekul,S.Hecht,W.Eisenreich, S.Gerhardt,A.Bacher,F.Rohdich

Key ref:

S.Steinbacher et al. (2002). Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids. J Mol Biol, 316, 79-88. PubMed id: 11829504 DOI: 10.1006/jmbi.2001.5341

Date:

22-Jul-04 Release date: 31-Aug-04

Protein chain

P62617  (ISPF_ECOLI) -  2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase from Escherichia coli (strain K12)

Seq: 159 a.a.

Struc: 155 a.a.

Enzyme reactions

• Enzyme class: E.C.4.6.1.12 - 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase.
• Reaction: 4-CDP-2-C-methyl-D-erythritol 2-phosphate = 2-C-methyl-D-erythritol 2,4- cyclic diphosphate + CMP
• Cofactor: Mn(2+) or Mg(2+)

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

Key reference

DOI no: 10.1006/jmbi.2001.5341

J Mol Biol 316:79-88 (2002)

PubMed id: 11829504

Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids.

S.Steinbacher, J.Kaiser, J.Wungsintaweekul, S.Hecht, W.Eisenreich, S.Gerhardt, A.Bacher, F.Rohdich.

ABSTRACT

Isoprenoids are biosynthesized from isopentenyl diphosphate and the isomeric dimethylallyl diphosphate via the mevalonate pathway or a mevalonate-independent pathway that was identified during the last decade. The non-mevalonate pathway is present in many bacteria, some algae and in certain protozoa such as the malaria parasite Plasmodium falciparum and in the plastids of higher plants, but not in mammals and archaea. Therefore, these enzymes have been recognised as promising drug targets. We report the crystal structure of Escherichia coli 2C- methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), which converts 4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate into 2C-methyl-d-erythritol 2,4-cyclodiphosphate and CMP in a Mg-dependent reaction. The protein forms homotrimers that tightly bind one zinc ion per subunit at the active site, which helps to position the substrate for direct attack of the 2-phosphate group on the beta-phosphate.

Selected figure(s)

Figure 1.
Figure 1. Non-mevalonate pathway of isopentenyl and dimethylallyldiphosphate biosynthesis. (a) Pyruvate and glyceraldehyde 3-phosphate are condensed to (b) 1-deoxy- Image -xylulose 5-phosphate, which is converted into (c) 2C-methyl- Image -erythritol 4-phosphate. Condensation with CTP yields (d) 4-diphosphocytidyl-2C-methyl- Image -erythritol, which is converted into (d) 4-diphosphocytidyl-2C-methyl- Image -erythritol 2-phosphate. The last step identified so far is the cyclisation of the latter to (f) 2C-methyl- Image -erythritol 2,4-cyclodiphosphate by IspF.

Figure 4.
Figure 4. Omit electron density for bound substrate and product molecules contoured at 2.5s (stereo view). All complexes were prepared by soaking. (a) Product complex with bound CMP and 2C-methyl- Image -erythritol 2,4-cyclodiphosphate (data set Prod). (b) Substrate complex with bound 4-diphosphocytidyl-2C-methyl- Image -erythritol 2-phosphate and zinc removed with EDTA; the green ball represents the zinc position in the active enzyme (data set CDP-MEP). (c) Complex with 4-diphosphocytidyl-2C-methyl- Image -erythritol (data set CDP-ME). (d) Complex with MgCDP; the Mg ion bridges the a and b-phosphate groups of CDP (data set MgCDP).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 316, 79-88) copyright 2002.

Figures were selected by an automated process.