1pv8
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Porphobilinogen synthase (PBGS) catalyzes the first common step in the | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Breinig, S.]] | [[Category: Breinig, S.]] | ||
[[Category: Fairman, R.]] | [[Category: Fairman, R.]] | ||
| - | [[Category: Jaffe, E | + | [[Category: Jaffe, E K.]] |
[[Category: Kervinen, J.]] | [[Category: Kervinen, J.]] | ||
[[Category: Stith, L.]] | [[Category: Stith, L.]] | ||
| - | [[Category: Wasson, A | + | [[Category: Wasson, A S.]] |
[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
[[Category: Zdanov, A.]] | [[Category: Zdanov, A.]] | ||
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[[Category: tetrapyrrole biosynthesis]] | [[Category: tetrapyrrole biosynthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:32:51 2008'' |
Revision as of 12:32, 21 February 2008
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Crystal structure of a low activity F12L mutant of human phorphobilinogen synthase
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Lead poisoning, susceptibility to OMIM:[125270], Porphyria, acute hepatic OMIM:[125270]
About 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.
Reference
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
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