3EQ1

The Crystal Structure of Human Porphobilinogen Deaminase at 2.8A resolution

Summary for 3EQ1

• Entry DOI: 10.2210/pdb3eq1/pdb
• Descriptor: Porphobilinogen deaminase, 3-[5-{[3-(2-carboxyethyl)-4-(carboxymethyl)-5-methyl-1H-pyrrol-2-yl]methyl}-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acid, SULFATE ION (3 entities in total)
• Functional Keywords: alpha and beta protein, alternative splicing, cytoplasm, disease mutation, heme biosynthesis, porphyrin biosynthesis, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm (Probable): P08397
• Total number of polymer chains: 2
• Total formula weight: 80221.16

Authors

Kolstoe, S.E.,Gill, R.,Mohammed, F.,Wood, S.P. (deposition date: 2008-09-30, release date: 2009-03-03, Last modification date: 2023-11-01)

Primary citation

Gill, R.,Kolstoe, S.E.,Mohammed, F.,Al D-Bass, A.,Mosely, J.E.,Sarwar, M.,Cooper, J.B.,Wood, S.P.,Shoolingin-Jordan, P.M.
Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria
Biochem.J., 420:17-25, 2009

PubMed 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.

PubMed: 19207107
DOI: 10.1042/BJ20082077

Experimental method

X-RAY DIFFRACTION (2.8 Å)