1PV8

Crystal structure of a low activity F12L mutant of human porphobilinogen synthase

Summary for 1PV8

• Entry DOI: 10.2210/pdb1pv8/pdb
• Descriptor: Delta-aminolevulinic acid dehydratase, ZINC ION, 3-(2-AMINOETHYL)-4-(AMINOMETHYL)HEPTANEDIOIC ACID, ... (4 entities in total)
• Functional Keywords: porphobilinogen synthase, tetrapyrrole biosynthesis, reaction intermediate, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 72972.77

Authors

Breinig, S.,Kervinen, J.,Stith, L.,Wasson, A.S.,Fairman, R.,Wlodawer, A.,Zdanov, A.,Jaffe, E.K. (deposition date: 2003-06-26, release date: 2003-09-09, Last modification date: 2024-12-25)

Primary citation

Breinig, S.,Kervinen, J.,Stith, L.,Wasson, A.S.,Fairman, R.,Wlodawer, A.,Zdanov, A.,Jaffe, E.K.
Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.
Nat.Struct.Biol., 10:757-763, 2003

PubMed Abstract: 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.

PubMed: 12897770
DOI: 10.1038/nsb963

Experimental method

X-RAY DIFFRACTION (2.2 Å)