PDBsum entry 1d0s

Transferase

PDB id: 1d0s

Contents

Protein chain

346 a.a. *

Ligands

PO4

DMD

Waters ×132

* Residue conservation analysis

PDB id:

1d0s

Name:

Transferase

Title:

Crystal structure of nicotinate mononucleotide : 5,6- dimethylbenzimidazole phosphoribosyltransferase (cobt) from salmonella typhimurium complexed with 5, 6-dimethylbenzimidazole

Structure:

Nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase. Chain: a. Ec: 2.4.2.21

Source:

Salmonella typhimurium. Organism_taxid: 602

Biol. unit:

Dimer (from PDB file)

Resolution:

1.90Å R-factor: 0.172

Authors:

C.-G.Cheong,J.C.Escalante-Semerena,I.Rayment

Key ref:

C.G.Cheong et al. (1999). The three-dimensional structures of nicotinate mononucleotide:5,6- dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium complexed with 5,6-dimethybenzimidazole and its reaction products determined to 1.9 A resolution. Biochemistry, 38, 16125-16135. PubMed id: 10587435 DOI: 10.1021/bi991752c

Date:

14-Sep-99 Release date: 29-Dec-99

Protein chain

Q05603  (COBT_SALTY) -  Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 356 a.a.

Struc: 346 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.4.2.21 - nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase.
• Pathway: Corrin Biosynthesis (part 8)
• Reaction: 5,6-dimethylbenzimidazole + nicotinate beta-D-ribonucleotide = alpha- ribazole 5'-phosphate + nicotinate + H⁺

5,6-dimethylbenzimidazole (Bound ligand (Het Group name = DMD) corresponds exactly) + nicotinate beta-D-ribonucleotide = alpha- ribazole 5'-phosphate + nicotinate + H(+)

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

reference

DOI no: 10.1021/bi991752c

Biochemistry 38:16125-16135 (1999)

PubMed id: 10587435

The three-dimensional structures of nicotinate mononucleotide:5,6- dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium complexed with 5,6-dimethybenzimidazole and its reaction products determined to 1.9 A resolution.

C.G.Cheong, J.C.Escalante-Semerena, I.Rayment.

ABSTRACT

Nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella typhimurium plays a central role in the synthesis of alpha-ribazole, which is a key component of the lower ligand of cobalamin. Two X-ray structures of CobT are reported here at 1.9 A resolution. First, a complex of CobT with 5,6-dimethylbenzimidazole, and second, a complex of CobT with its reaction products, nicotinate and alpha-ribazole-5'-phosphate. CobT was cocrystallized with 5,6-dimethylbenzimidazole (DMB) in the space group P2(1)2(1)2 with unit cell dimensions of a = 72.1 A, b = 90.2 A, and c = 47.5 A and one protomer per asymmetric unit. Subsequently, the crystals containing DMB were soaked in nicotinate mononucleotide whereupon the physiological reaction occurred in the crystal lattice to yield nicotinate and alpha-ribazole-5'-phosphate. These studies show that CobT is a dimer where each subunit consists of two domains. The large domain is dominated by a parallel six-stranded beta-sheet with connecting alpha-helices that exhibit the topology of a Rossmann fold. The small domain is made from components of the N- and C-terminal sections of the polypeptide chain and contains a three-helix bundle. The fold of CobT is unrelated to the type I and II phosphoribosylpyrophosphate dependent transferases and does not appear to be related to any other protein whose structure is known. The enzyme active site is located in a large cavity formed by the loops at the C-terminal ends of the beta-strands and the small domain of the neighboring subunit. DMB binds in a hydrophobic pocket created in part by the neighboring small domain. This is consistent with the broad specificity of this enzyme for aromatic substrates [Trzebiatowski, J. R., Escalante-Semerena (1997) J. Biol. Chem. 272, 17662-17667]. The binding site for DMB suggests that Glu317 is the catalytic base required for the reaction. The remainder of the cavity binds the nicotinate and ribose-5'-phosphate moieties, which are nestled within the loops at the ends of the beta-strands. Interestingly, the orientation of the substrate and products are opposite from that expected for a Rossmann fold.