Nature Structural Biology
10, 757 - 763 (2003)
Published online: 3 August 2003; | doi:10.1038/nsb963
Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthaseSabine Breinig1, Jukka Kervinen2, Linda Stith1, Andrew S Wasson3, Robert Fairman3, Alexander Wlodawer4, Alexander Zdanov4
& Eileen K Jaffe11
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111-2497, USA. 2
3-Dimensional Pharmaceuticals, Inc., 665 Stockton Drive, Exton, Pennsylvania 19341, USA. 3
Department of Biology, Haverford College, 370 Lancaster Avenue, Haverford, Pennsylvania 19041, USA. 4
Macromolecular Crystallography Laboratory, NCI-Frederick, Frederick, Maryland 21702, USA.
Correspondence should be addressed to Eileen K Jaffe ek_jaffe@fccc.eduPorphobilinogen 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.
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REFERENCE
Haem Biosynthesis
Nature Encyclopaedia of Life Sciences
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