3ecr is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[HEM3_HUMAN] Defects in HMBS are the cause of acute intermittent porphyria (AIP) [MIM:176000]. AIP is a form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by acute attacks of neurological dysfunctions with abdominal pain, hypertension, tachycardia, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] [:][28][29][30][31][32][33]
Function
[HEM3_HUMAN] Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Acute intermittent porphyria (AIP), an inherited disease of heme biosynthesis, is one of the most common types of porphyria. Reduced activity of the enzyme porphobilinogen deaminase (PBGD), which catalyzes the sequential condensation of 4 molecules of porphobilinogen to yield preuroporphyrinogen, has been linked to the symptoms of AIP. We have determined the 3-dimensional structure of human PBGD at 2.2 A resolution. Analysis of the structure revealed a dipyrromethane cofactor molecule covalently linked to C261, sitting in a positively charged cleft region. In addition to the critical catalytic D99, a number of other residues are seen hydrogen bonded to the cofactor and play a role in catalysis. Sequential entry of 4 pyrrole molecules into the active site is accomplished by movement of the domains around the hinges. H120P mutation resulted in an inactive enzyme, supporting the role of H120 as a hinge residue. Interestingly, some of the mutations of the human PBGD documented in patients suffering from AIP are located far away from the active site. The structure provides insights into the mechanism of action of PBGD at the molecular level and could aid the development of potential drugs for the up-regulation of PBGD activity in AIP.
Structural insight into acute intermittent porphyria.,Song G, Li Y, Cheng C, Zhao Y, Gao A, Zhang R, Joachimiak A, Shaw N, Liu ZJ FASEB J. 2009 Feb;23(2):396-404. Epub 2008 Oct 20. PMID:18936296[34]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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↑Song G, Li Y, Cheng C, Zhao Y, Gao A, Zhang R, Joachimiak A, Shaw N, Liu ZJ. Structural insight into acute intermittent porphyria. FASEB J. 2009 Feb;23(2):396-404. Epub 2008 Oct 20. PMID:18936296 doi:10.1096/fj.08-115469
