PDBsum entry 1iv2

Lyase

PDB id

1iv2

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Contents

			Protein chains

					(+ 0 more) 150 a.a. *

			Ligands

					CDP ×6

			Metals

					_MG ×12

			Waters ×509

* Residue conservation analysis

PDB id:

1iv2

Links

Name:

Lyase

Title:

Structure of 2c-methyl-d-erythritol-2,4-cyclodiphosphate synthase (bound form cdp)

Structure:

2-c-methyl-d-erythritol 2,4-cyclodiphosphate synthase. Chain: a, b, c, d, e, f. Engineered: yes. Mutation: yes

Source:

Thermus thermophilus. Organism_taxid: 274. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Trimer (from PQS)

Resolution:

1.55Å

R-factor:

0.197

R-free:

0.272

Authors:

H.Kishida,T.Wada,S.Unzai,T.Kuzuyama,T.Terada,M.Sirouzu,S.Yokoyama, J.R.H.Tame,S.-Y.Park,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

H.Kishida et al. (2003). Structure and catalytic mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECDP) synthase, an enzyme in the non-mevalonate pathway of isoprenoid synthesis. Acta Crystallogr D Biol Crystallogr, 59, 23-31. PubMed id: 12499535

Date:

11-Mar-02

Release date:

11-Sep-02

PROCHECK

	Headers

	References

Protein chains

Q8RQP5 (ISPF_THET8) - 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: Struc:					152 a.a. 150 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 3 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.4.6.1.12 - 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

4-CDP-2-C-methyl-D-erythritol 2-phosphate = 2-C-methyl-D-erythritol 2,4- cyclic diphosphate + CMP

4-CDP-2-C-methyl-D-erythritol 2-phosphate

2-C-methyl-D-erythritol 2,4- cyclic diphosphate

CMP
Bound ligand (Het Group name = CDP)
matches with 84.00% similarity

Cofactor:

Mn(2+) or Mg(2+)

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

Key reference

	Acta Crystallogr D Biol Crystallogr 59:23-31 (2003)
PubMed id: 12499535

Structure and catalytic mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECDP) synthase, an enzyme in the non-mevalonate pathway of isoprenoid synthesis.
H.Kishida, T.Wada, S.Unzai, T.Kuzuyama, M.Takagi, T.Terada, M.Shirouzu, S.Yokoyama, J.R.Tame, S.Y.Park.

ABSTRACT

Precursors for isoprenoid synthesis are essential in all organisms. These compounds are synthesized by one of two known routes: the well characterized mevalonate pathway or a recently discovered non-mevalonate route which is used in many bacteria and human pathogens. Since the second pathway is both vital and unlike any found in humans, enzymes catalysing reactions along this synthetic route are possible drug targets. The structure of one such enzyme from the thermophilic bacterium Thermus thermophilus has been solved to high resolution in the presence of substrate and with a substrate analogue. Enzyme co-crystallized with substrate shows only one product, cytosine monophosphate (CMP), in the active site. At the high resolution of the refinement (1.6 A) the positions and coordination of the magnesium ions in the active site are clearly seen.

Literature references that cite this PDB file's key reference

PubMed id

Reference

18793870

H.Eoh, P.J.Brennan, and D.C.Crick (2009).
The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target.

Tuberculosis (Edinb), 89, 1.

19320487

N.L.Ramsden, L.Buetow, A.Dawson, L.A.Kemp, V.Ulaganathan, R.Brenk, G.Klebe, and W.N.Hunter (2009).
A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy.

J Med Chem, 52, 2531-2542.

PDB codes:

3elc 3eor 3ern 3esj 3fba

17660251

B.M.Calisto, J.Perez-Gil, M.Bergua, J.Querol-Audi, I.Fita, and S.Imperial (2007).
Biosynthesis of isoprenoids in plants: structure of the 2C-methyl-D-erithrytol 2,4-cyclodiphosphate synthase from Arabidopsis thaliana. Comparison with the bacterial enzymes.

Protein Sci, 16, 2082-2088.

PDB code:

2pmp

17956607

L.Buetow, A.C.Brown, T.Parish, and W.N.Hunter (2007).
The structure of Mycobacteria 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery.

BMC Struct Biol, 7, 68.

PDB code:

2uzh

17442674

W.N.Hunter (2007).
The non-mevalonate pathway of isoprenoid precursor biosynthesis.

J Biol Chem, 282, 21573-21577.

16511114

T.Sgraja, L.E.Kemp, N.Ramsden, and W.N.Hunter (2005).
A double mutation of Escherichia coli2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase disrupts six hydrogen bonds with, yet fails to prevent binding of, an isoprenoid diphosphate.

Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 625-629.

PDB code:

1yqn

15558583

Y.Qi, and N.V.Grishin (2005).
Structural classification of thioredoxin-like fold proteins.

Proteins, 58, 376-388.

15466439

M.Gabrielsen, C.S.Bond, I.Hallyburton, S.Hecht, A.Bacher, W.Eisenreich, F.Rohdich, and W.N.Hunter (2004).
Hexameric assembly of the bifunctional methylerythritol 2,4-cyclodiphosphate synthase and protein-protein associations in the deoxy-xylulose-dependent pathway of isoprenoid precursor biosynthesis.

J Biol Chem, 279, 52753-52761.

PDB codes:

1w55 1w57

12878729

L.Miallau, M.S.Alphey, L.E.Kemp, G.A.Leonard, S.M.McSweeney, S.Hecht, A.Bacher, W.Eisenreich, F.Rohdich, and W.N.Hunter (2003).
Biosynthesis of isoprenoids: crystal structure of 4-diphosphocytidyl-2C-methyl-D-erythritol kinase.

Proc Natl Acad Sci U S A, 100, 9173-9178.

PDB code:

1oj4

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.