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spinqualitylabelsall models PDB ID 3eq1 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
3eq1, resolution 2.80Å ()
Ligands:	,
Activity:	Hydroxymethylbilane synthase, with EC number 2.5.1.61
Structural annotation: Resources: InterPro : Ipr000860 Pfam : PF01379, PF03900 UniProt : P08397
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

Porphobilinogen deaminase (PBGD) also known as Hydroxymethylbilane synthase, is a monomeric polypeptide and is the third enzyme in the heme biosynthesis pathways in mammals^[1]. It catalyses the polymerization of four porphobilinogen molecules to yield hydroxymethylbilane, a precursor in the formation of Porphyrin^[2]. Porphobilinogen deaminases are able to form surprisingly stable enzyme-substrate complexes with up to four pyrrole substrates interacting with the active site, a feature unique to the group of enzymes^[3]. , a cofactor unique to porphobilinogen deaminases, is thought to stabilize these interactions at each of the two active domains^[2]. Mutations in the human PBGD (hPBGD) gene are responsible for the condition Acute Intermittent Porphyria (AIP) in humans^[1].

Porphobilinogen deaminase

Contents 1 Porphobilinogen deaminase 1.1 Structure 1.2 Function 1.2.1 Mechanism 1.2.2 Acute Intermittent Porphyria 1.3 Importance of hPBGD 1.4 References

Structure

spinqualitylabelsall models PDB ID 3eq1 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

PBGD is a monomeric three-domain polypeptide with each domain consisting of approximately 110 amino acids. The human variant has an additional 29 residue loop in domain three that extends hydrogen bonding across domains one and three while E.coli PBGD is lacking this extended loop ^[1]. In the active site, a unique molecule known as interacts with porphobilinogen and anchors it in place^[1]. Ordered are also hydrogen bonded with Arg26 and Ser28 residues near the active site that are highly conserved amongst human and E.coli variants of PBGD^[1]. Although PBGD appears to have hydrogen bonding capabilities between two identical PBGD units, at physiological pH, these interactions account for a dimer interface of approximately 5% while average dimer interface between subunits is 16%^[1]. Therefore, it is generally assumed that this protein is active naturally as a monomeric enzyme, while the crystalline form is a homo-dimeric structure of two identical PBGD subunits^[1].

Function

Mechanism

Acute Intermittent Porphyria

Importance of hPBGD

References

1. ↑ ^{1.0 1.1 1.2 1.3 1.4 1.5 1.6} Gill R, Kolstoe SE, Mohammed F, Al D-Bass A, Mosely JE, Sarwar M, Cooper JB, Wood SP, Shoolingin-Jordan PM. Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria. Biochem J. 2009 Apr 28;420(1):17-25. PMID:19207107 doi:10.1042/BJ20082077
2. ↑ ^{2.0 2.1} Jordan PM, Warren MJ. Evidence for a dipyrromethane cofactor at the catalytic site of E. coli porphobilinogen deaminase. FEBS Lett. 1987 Dec 10;225(1-2):87-92. PMID:3079571
3. ↑ Anderson PM, Desnick RJ. Purification and properties of uroporphyrinogen I synthase from human erythrocytes. Identification of stable enzyme-substrate intermediates. J Biol Chem. 1980 Mar 10;255(5):1993-9. PMID:7354069