Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.
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.
Breinig
Sabine
S
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111-2497, USA.
Kervinen
Jukka
J
Stith
Linda
L
Wasson
Andrew S
AS
Fairman
Robert
R
Wlodawer
Alexander
A
Zdanov
Alexander
A
Jaffe
Eileen K
EK
D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002734:Chlorophyll / Q000737:chemistry; D006224:Cricetinae; D018360:Crystallography, X-Ray; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006418:Heme / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D010944:Plants / Q000378:metabolism; D000623:Porphobilinogen Synthase / Q000737:chemistry*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011758:Pyrroles; D045725:Tetrapyrroles; D014461:Ultracentrifugation
D011758:Pyrroles; D045725:Tetrapyrroles; D002734:Chlorophyll; D006418:Heme; D004492:Edetic Acid; D005982:Glutathione Transferase; D000623:Porphobilinogen Synthase; D008274:Magnesium