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| - | ='''Porphobilinogen Deaminase'''= | ||
{{STRUCTURE_3eq1 | PDB=3eq1 | SCENE= }} | {{STRUCTURE_3eq1 | PDB=3eq1 | SCENE= }} | ||
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Porphobilinogen deaminase (PBGD) also known as Hydroxymethylbilane synthase, is a monomeric polypeptide and is the third enzyme in the heme biosynthesis pathways in mammals<ref name="Raj">PMID: 19207107</ref>. It catalyses the polymerization of four porphobilinogen molecules to yield hydroxymethylbilane, a precursor in the formation of [[Porphyrin]]<ref name="Peter">PMID:3079571</ref>. 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<ref name="Anderson">PMID:7354069</ref>. <scene name='Sandbox_Reserved_349/Dpm/1'>Dipyrromethane (DPM)</scene>, a cofactor unique to porphobilinogen deaminases, is thought to stabilize these interactions at each of the two active domains<ref name="Peter">PMID:3079571</ref>. Mutations in the human PBGD gene are responsible for the condition Acute Intermittent Porphyria (AIP) in humans<ref name="Raj">PMID: 19207107</ref>. | Porphobilinogen deaminase (PBGD) also known as Hydroxymethylbilane synthase, is a monomeric polypeptide and is the third enzyme in the heme biosynthesis pathways in mammals<ref name="Raj">PMID: 19207107</ref>. It catalyses the polymerization of four porphobilinogen molecules to yield hydroxymethylbilane, a precursor in the formation of [[Porphyrin]]<ref name="Peter">PMID:3079571</ref>. 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<ref name="Anderson">PMID:7354069</ref>. <scene name='Sandbox_Reserved_349/Dpm/1'>Dipyrromethane (DPM)</scene>, a cofactor unique to porphobilinogen deaminases, is thought to stabilize these interactions at each of the two active domains<ref name="Peter">PMID:3079571</ref>. Mutations in the human PBGD gene are responsible for the condition Acute Intermittent Porphyria (AIP) in humans<ref name="Raj">PMID: 19207107</ref>. | ||
=Structure= | =Structure= | ||
Revision as of 22:11, 28 February 2011
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| 3eq1, resolution 2.80Å () | |||||||||
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| Ligands: | , | ||||||||
| Activity: | Hydroxymethylbilane synthase, with EC number 2.5.1.61 | ||||||||
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| 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 gene are responsible for the condition Acute Intermittent Porphyria (AIP) in humans[1].
Structure
Human PBGD is a three-domain polypeptide with each domain consisting of approximately 110 amino acids[1]. In the active site, a unique molecule known as interacts with porphobilinogen and anchors it in place[1]. Ordered sulfate ions 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 enyme[1].
Function
References
- ↑ 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
- ↑ 2.0 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
- ↑ 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
