1pv8
Crystal structure of a low activity F12L mutant of human phorphobilinogen synthase
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OverviewOverview
Porphobilinogen synthase (PBGS) catalyzes the first common step in the biosynthesis of tetrapyrroles (such as heme and chlorophyll). Although the predominant oligomeric form of this enzyme, as inferred from many crystal structures, is that of a homo-octamer, a rare human PBGS allele, F12L, reveals the presence of a hexameric form. Rearrangement of an N-terminal arm is responsible for this oligomeric switch, which results in profound changes in kinetic behavior. The structural transition between octamer and hexamer must proceed through an unparalleled equilibrium containing two different dimer structures. The allosteric magnesium, present in most PBGS, has a binding site in the octamer but not in the hexamer. The unprecedented structural rearrangement reported here relates to the allosteric regulation of PBGS and suggests that alternative PBGS oligomers may function in a magnesium-dependent regulation of tetrapyrrole biosynthesis in plants and some bacteria.
DiseaseDisease
Known diseases associated with this structure: Lead poisoning, susceptibility to OMIM:[125270], Porphyria, acute hepatic OMIM:[125270]
About this StructureAbout this Structure
1PV8 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Porphobilinogen synthase, with EC number 4.2.1.24 Full crystallographic information is available from OCA.
ReferenceReference
Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase., Breinig S, Kervinen J, Stith L, Wasson AS, Fairman R, Wlodawer A, Zdanov A, Jaffe EK, Nat Struct Biol. 2003 Sep;10(9):757-63. Epub 2003 Aug 3. PMID:12897770
Page seeded by OCA on Thu Feb 21 14:32:51 2008