PDBsum entry 1gqc

Transferase

PDB id: 1gqc

Contents

Protein chains

242 a.a. *

Ligands

CMK

C5P

Metals

_MG ×2

Waters ×267

* Residue conservation analysis

PDB id:

1gqc

Name:

Transferase

Title:

The structure of cmp:2-keto-3-deoxy-manno-octonic acid synthetase complexed with cmp-kdo at 100k

Structure:

3-deoxy-manno-octulosonate cytidylyltransferase. Chain: a, b. Synonym: cmp-kdo synthetase, cmp-2-keto-3-deoxyoctulosonic acid synthetase, cks. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Strain: k5. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.60Å R-factor: 0.178 R-free: 0.240

Authors:

S.Jelakovic,G.E.Schulz

Key ref:

S.Jelakovic and G.E.Schulz (2002). Catalytic mechanism of CMP:2-keto-3-deoxy-manno-octonic acid synthetase as derived from complexes with reaction educt and product. Biochemistry, 41, 1174-1181. PubMed id: 11802716 DOI: 10.1021/bi0119060

Date:

21-Nov-01 Release date: 11-Feb-02

Protein chains

P42216  (KPSU5_ECOLX) -  3-deoxy-manno-octulosonate cytidylyltransferase from Escherichia coli

Seq: 246 a.a.

Struc: 242 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.7.38 - 3-deoxy-manno-octulosonate cytidylyltransferase.
• Reaction: 3-deoxy-alpha-D-manno-oct-2-ulosonate + CTP = CMP-3-deoxy-beta-D-manno- octulosonate + diphosphate

3-deoxy-alpha-D-manno-oct-2-ulosonate + CTP (Bound ligand (Het Group name = CMK) matches with 47.73% similarity) = CMP-3-deoxy-beta-D-manno- octulosonate + diphosphate

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

Added reference

DOI no: 10.1021/bi0119060

Biochemistry 41:1174-1181 (2002)

PubMed id: 11802716

Catalytic mechanism of CMP:2-keto-3-deoxy-manno-octonic acid synthetase as derived from complexes with reaction educt and product.

S.Jelakovic, G.E.Schulz.

ABSTRACT

The activation of the sugar 2-keto-3-deoxy-manno-octonic acid (Kdo) is catalyzed by CMP-Kdo synthetase (EC 2.7.7.38) and results in a monophosphate diester with CMP. The enzyme is a pharmaceutical target because CMP-Kdo is required for the biosynthesis of lipopolysaccharides that are vital for Gram-negative bacteria. We have established the structures of an enzyme complex with the educt CTP and of a complex with the product CMP-Kdo by X-ray diffraction analyses at 100 K, both at 2.6 A resolution. The N-terminal domains of the dimeric enzyme bind CTP in a peculiar nucleotide-binding fold with the beta- and gamma-phosphates located at the so-called "PP-loop", whereas the C-terminal domains participate in Kdo binding and in the dimer interface. The unstable nucleotide-sugar CMP-Kdo was produced in a crystal and stabilized by freezing to 100 K. Its formation is accompanied by an induced fit involving mainchain displacements in the 2 A range. The observed binding conformations together with the amino acid conservation pattern during evolution and the putative location of the required Mg(2+) ion suggest a reaction pathway. The enzyme is structurally homologous to the CMP-N-acetylneuraminic acid synthetases in all parts except for the dimer interface. Moreover, the chainfold and the substrate-binding positions resemble those of other enzymes processing nucleotide sugars.