PDBsum entry 4mlv

Transferase

PDB id: 4mlv

Contents

Protein chain

290 a.a.

Ligands

DPM-29P

ACY

Waters ×325

PDB id:

4mlv

Name:

Transferase

Title:

Crystal structure of bacillus megaterium porphobilinogen deaminase

Structure:

Porphobilinogen deaminase. Chain: a. Fragment: porphobilinogen deaminase. Synonym: pbg, hydroxymethylbilane synthase, pre-uroporphyrinogen synthase. Engineered: yes

Source:

Bacillus megaterium. Organism_taxid: 1404. Gene: hemc. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.46Å R-factor: 0.143 R-free: 0.186

Authors:

N.Azim,E.Deery,M.J.Warren,P.Erskine,J.B.Cooper,A.Coker,S.P.Wood, M.Akhtar

Key ref:

N.Azim et al. (2014). Structural evidence for the partially oxidized dipyrromethene and dipyrromethanone forms of the cofactor of porphobilinogen deaminase: structures of the Bacillus megaterium enzyme at near-atomic resolution. Acta Crystallogr D Biol Crystallogr, 70, 744-751. PubMed id: 24598743 DOI: 10.1107/S139900471303294X

Date:

06-Sep-13 Release date: 02-Apr-14

Protein chain

Q8GCA8  (Q8GCA8_PRIMG) -  Porphobilinogen deaminase from Priestia megaterium

Seq: 310 a.a.

Struc: 290 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.61 - hydroxymethylbilane synthase.
• Pathway: Porphyrin Biosynthesis (early stages)
• Reaction: 4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH4⁺

4 × porphobilinogen + H2O = hydroxymethylbilane (Bound ligand (Het Group name = DPM) matches with 49.18% similarity) + 4 × NH4(+)

• Cofactor: Dipyrromethane

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

Added reference

DOI no: 10.1107/S139900471303294X

Acta Crystallogr D Biol Crystallogr 70:744-751 (2014)

PubMed id: 24598743

Structural evidence for the partially oxidized dipyrromethene and dipyrromethanone forms of the cofactor of porphobilinogen deaminase: structures of the Bacillus megaterium enzyme at near-atomic resolution.

N.Azim, E.Deery, M.J.Warren, B.A.Wolfenden, P.Erskine, J.B.Cooper, A.Coker, S.P.Wood, M.Akhtar.

ABSTRACT

The enzyme porphobilinogen deaminase (PBGD; hydroxymethylbilane synthase; EC 2.5.1.61) catalyses an early step of the tetrapyrrole-biosynthesis pathway in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole. The enzyme possesses a dipyrromethane cofactor, which is covalently linked by a thioether bridge to an invariant cysteine residue (Cys241 in the Bacillus megaterium enzyme). The cofactor is extended during the reaction by the sequential addition of the four substrate molecules, which are released as a linear tetrapyrrole product. Expression in Escherichia coli of a His-tagged form of B. megaterium PBGD has permitted the X-ray analysis of the enzyme from this species at high resolution, showing that the cofactor becomes progressively oxidized to the dipyrromethene and dipyrromethanone forms. In previously solved PBGD structures, the oxidized cofactor is in the dipyromethenone form, in which both pyrrole rings are approximately coplanar. In contrast, the oxidized cofactor in the B. megaterium enzyme appears to be in the dipyrromethanone form, in which the C atom at the bridging α-position of the outer pyrrole ring is very clearly in a tetrahedral configuration. It is suggested that the pink colour of the freshly purified protein is owing to the presence of the dipyrromethene form of the cofactor which, in the structure reported here, adopts the same conformation as the fully reduced dipyrromethane form.