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Your search keyword '"Myers, Rebecca S."' showing total 11 results
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11 results on '"Myers, Rebecca S."'

1. Reaction coupling through interdomain contacts in imidazole glycerol phosphate synthase

Author

Myers, Rebecca S., Amaro, Rommie E., Luthey-Schulten, Zaida A., and Davisson, V. Jo

Subjects
Imidazole -- Chemical properties, Imidazole -- Structure, Glycerin -- Chemical properties, Glycerin -- Structure, Glycerol -- Chemical properties, Glycerol -- Structure, Brewer's yeast -- Research, Biological sciences, Chemistry
Abstract

The interdomain contacts observed in the crystal structure of S. cerevisiae imidazole glycerol phosphate synthase and a network of amino acids that mediate the [(5'-phosphoribulosyl)-formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PRFAR) binding signal to the glutaminase active site is analyzed. The amino acids, D359 from the cyclase domain, and K196, a residue adjacent to the glutaminase active site, form the only conserved interdomain salt bridge in the interface region.

Published
2005

6. A network of conserved interactions regulates the allosteric signal in a glutamine amidotransferase

Author

Amaro, Rommie E., Myers, Rebecca S., Davisson, V. Jo, Luthey-Schulten, Zaida A., and Sethi, Anurag

Subjects
Allosteric enzymes -- Research, Glutamine synthetase -- Research, Protein-protein interactions -- Research, Biological sciences, Chemistry
Abstract

The mechanism of allosteric regulation in imidazole glycerol phosphate (IGP) synthase is probed by combining equilibrium and steered molecular dynamics (SMD) simulations with principal component correlation analyses. Analyses of IGP synthase disclosed a conserved network of interactions leading from the effector-binding site to the glutaminase active site.

Published
2007

8. Crystal structure of Methanobacterium thermoautotrophicum phosphoribosyl-AMP cyclohydrolase HisI

Author

Sivaraman, J., Myers, Rebecca S., Boju, Lorena, Cygler, Miroslaw, Schrag, Joseph D., Sulea, Traian, and Davisson, V. Jo

Subjects
Hydrolases -- Research, Methanobacteriaceae -- Research, Enzymes -- Research, Crystals -- Structure, Crystals -- Research, Biological sciences, Chemistry
Abstract

The crystal structure of the phosphoribosyl cyclohydrolase, HisI, from the archaea Methanobacterium thermoautotrophicum is reported. Analysis of the three-dimensional structure in light of the biochemical characterization of the homologous Methanobacterium vannielli enzyme identifies the active site and the likely Zn(super 2+)- and Mg(super 2+)- binding sites.

Published
2005

9. Substrate-induced changes in the ammonia channel for imidazole glycerol phosphate synthase

Author

Myers, Rebecca S., Jensen, Jordan R., Deras, Ina L., Smith, Janet L., and Davisson, V. Jo

Subjects
Protein binding -- Analysis, Enzymes -- Structure-activity relationship, Biological sciences, Chemistry
Abstract

The structure and function of imidazole glycerol phosphate synthase shows that the transfer of ammonia from the glutaminase site occurs via the (beta/alpha)(sub)8 core and that amino acid residue K258 is critical for substrate binding and overall stoichiometry of the enzyme reaction. Data indicate that substrate binding induces conformational changes at the base of the (beta/alpha)(sub)8 core.

Published
2003

10. Toward understanding the mechanism of the complex cyclization reaction catalyzed by imidazole glycerolphosphate synthase: crystal structures of a ternary complex and the free enzyme

Author

Chaudhuri, Barnali N., Lange, Stephanie C., Myers, Rebecca S., Davisson, V. Jo, and Smith, Janet L.

Subjects
Mechanical chemistry -- Research, Ring formation (Chemistry) -- Analysis, Crystals -- Analysis, Binding sites (Biochemistry) -- Analysis, Biological sciences, Chemistry
Abstract

Comparison of the free, acivicin-, and 6-diazo-5-oxo-L-norleucine inactivated crystal structures of the glutaminase active site shows structural changes accompanying activation of the imidazole glycerolphosphate synthase. Furthermore, the N(sup)1-(5'-phosphoribulosyl)-formimino-5-aminoimidazole-4-carboxamide ribonucleotide-bound and -free forms of the enzyme suggest crosstalk between active sites.

Published
2003

11. Crystal Structure of Imidazole Glycerol Phosphate Synthase A Tunnel through a (β/α)8 Barrel Joins Two Active Sites

Author

Chaudhuri, Barnali N, Lange, Stephanie C, Myers, Rebecca S, Chittur, Sridar V, Davisson, V.Jo, and Smith, Janet L

Subjects
histidine biosynthesis, glutamine amidotransferase, ammonia tunnel, intermediate channeling
Abstract

Background: Imidazole glycerol phosphate synthase catalyzes a two-step reaction of histidine biosynthesis at the bifurcation point with the purine de novo pathway. The enzyme is a new example of intermediate channeling by glutamine amidotransferases in which ammonia generated by hydrolysis of glutamine is channeled to a second active site where it acts as a nucleophile. In this case, ammonia reacts in a cyclase domain to produce imidazole glycerol phosphate and an intermediate of purine biosynthesis. The enzyme is also a potential target for drug and herbicide development since the histidine pathway does not occur in mammals.Results: The 2.1 Å crystal structure of imidazole glycerol phosphate synthase from yeast reveals extensive interaction of the glutaminase and cyclase catalytic domains. At the domain interface, the glutaminase active site points into the bottom of the (β/α)8 barrel of the cyclase domain. An ammonia tunnel through the (β/α)8 barrel connects the glutaminase docking site at the bottom to the cyclase active site at the top. A conserved “gate” of four charged residues controls access to the tunnel.Conclusions: This is the first structure in which all the components of the ubiquitous (β/α)8 barrel fold, top, bottom, and interior, take part in enzymatic function. Intimate contacts between the barrel domain and the glutaminase active site appear to be poised for crosstalk between catalytic centers in response to substrate binding at the cyclase active site. The structure provides a number of potential sites for inhibitor development in the active sites and in a conserved interdomain cavity.

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