PDBsum entry 3eq1

Transferase

PDB id: 3eq1

Contents

Protein chains

312 a.a. *

Ligands

DPM ×2

SO4 ×7

* Residue conservation analysis

PDB id:

3eq1

Name:

Transferase

Title:

The crystal structure of human porphobilinogen deaminase at 2.8a resolution

Structure:

Porphobilinogen deaminase. Chain: a, b. Fragment: unp residues 19-356. Synonym: pbg-d, pre-uroporphyrinogen synthase, hydroxymethylbilane synthase, hmbs. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.80Å R-factor: 0.262 R-free: 0.289

Authors:

S.E.Kolstoe,R.Gill,F.Mohammed,S.P.Wood

Key ref:

R.Gill et al. (2009). Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria. Biochem J, 420, 17-25. PubMed id: 19207107

Date:

30-Sep-08 Release date: 03-Mar-09

Protein chains

P08397  (HEM3_HUMAN) -  Porphobilinogen deaminase from Homo sapiens

Seq: 361 a.a.

Struc: 312 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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

Biochem J 420:17-25 (2009)

PubMed id: 19207107

Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria.

R.Gill, S.E.Kolstoe, F.Mohammed, A.Al D-Bass, J.E.Mosely, M.Sarwar, J.B.Cooper, S.P.Wood, P.M.Shoolingin-Jordan.

ABSTRACT

Mutations in the human PBGD (porphobilinogen deaminase) gene cause the inherited defect AIP (acute intermittent porphyria). In the present study we report the structure of the human uPBGD (ubiquitous PBGD) mutant, R167Q, that has been determined by X-ray crystallography and refined to 2.8 A (1 A=0.1 nm) resolution (Rfactor=0.26, Rfree=0.29). The protein crystallized in space group P2(1)2(1)2 with two molecules in the asymmetric unit (a=81.0 A, b=104.4 A and c=109.7 A). Phases were obtained by molecular replacement using the Escherichia coli PBGD structure as a search model. The human enzyme is composed of three domains each of approx. 110 amino acids and possesses a dipyrromethane cofactor at the active site, which is located between domains 1 and 2. An ordered sulfate ion is hydrogen-bonded to Arg26 and Ser28 at the proposed substrate-binding site in domain 1. An insert of 29 amino acid residues, present only in mammalian PBGD enzymes, has been modelled into domain 3 where it extends helix alpha2(3) and forms a beta-hairpin structure that contributes to a continuous hydrogen-bonding network spanning domains 1 and 3. The structural and functional implications of the R167Q mutation and other mutations that result in AIP are discussed.