E K Jaffe

..The data support a novel model where a high affinity lead site is a hybrid of the ZnA and ZnB sites. We propose that the lone electron pair of Pb(II) precludes Pb(II) to function in PBGS catalysis...

..The reaction appears to stall at a covalently bound almost-product intermediate that is poised for breakdown to product upon binding of a substrate molecule to an adjacent active site and a subsequent conformational change...

..The phylogenetic distribution of PBGS metal ion utilization suggests that the primordial PBGS required zinc and supports a hypothesis that the loss of the zinc site was concurrent with the advent of oxygenic photosynthesis...

..The R221K mutation was inserted into wild type and chimeric human PBGS and found to further reduce the activity of both, illustrating the subtle nature of the role of this residue...

..A comparison of these with other PBGS structures identifies highly conserved active site water molecules, which are isolated from bulk solvent and implicated as proton acceptors in the PBGS-catalyzed reaction...

..coli numbering). This is the first structure to show inhibitor binding at the second of two substrate-binding sites...

..Thus, formation of the lysine to ALA Schiff base is not required to initiate the asymmetry that results in half-site reactivity...

..The addition of unlabeled or 1-13C-labeled ALA does not significantly affect the Mn(II) EPR spectra.(ABSTRACT TRUNCATED AT 250 WORDS)..

..However, there was no differential displacement of Zn(II) by Pb(II) between K59 and N59, and simple Pb(II) inhibition studies revealed no allelic difference...

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..abstract truncated at 250 words)..

..Li, and M. P. Timko (1991) J. Biol. Chem. 266, 17060-17066]. This work lays the foundation for identification of functional amino acids based on the sequence similarities between PBGS from bacterial, plant, and mammalian sources...

..Data support the hypothesis that human PBGS hexamer stabilization may explain these side effects. The current work identifies allosteric ligands of human PBGS and, thus, identifies human PBGS as a medically relevant allosteric enzyme...

..We propose that the disequilibrium of morpheein assemblies broadens the definition of conformational diseases beyond the prion disorders and that ALAD porphyria is the first example of a morpheein-based conformational disease...

..It is proposed here that the behavior of some other allosteric enzymes reflect dynamic morpheein equilibrium systems and six candidate proteins are enumerated...

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..The distinct phylogenetic, enzymatic, and structural features of apicomplexan PBGS offer scope for developing selective inhibitors of the parasite enzyme based on its quaternary structure characteristics...

..The metastable nature of the R240A hexamer supports the hypothesis that octameric and hexameric morpheeins of PBGS are very close in energy. W19A assembles into a mixture of dimers, which appear to be stable...

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..This observation illustrates that the assembly and disassembly of oligomeric proteins can be facilitated by the protein motions that accompany enzymatic catalysis...

..5/subunit. This result reveals a structural basis for half-of-the-sites metal binding that is consistent with a reciprocating motion model for function of oligomeric PBGS...

..We propose that this strategy for inhibitor discovery can be applied to other proteins that use the morpheein model for allosteric regulation...

..This case represents the molecular analysis of the ALAD gene defects in the first case of ADP identified in North America, who is a compound heterozygote for two novel ALAD gene defects...

..This paper reports new information on the metal ion independence and quaternary structure of PBGS from the photosynthetic bacterium Rhodobacter capsulatus...