Abstract

The objectives of the studies proposed herein are to develop techniques for the study of phosphoryl transfer mechanisms and to apply these techniques along with existing ones to detailed characterization of the catalytic mechanisms of selected enzymes which catalyze intra- and inter-molecular phosphoryl transfer reactions. The techniques that we wish to explore will involve, (i) the preparation of new M(III) complexes of ATP, ADP and PP to be used to probe enzyme substrate specificity and chemical mechanism, and (ii) the preparation and stereochemical assignment of the diastereomers of Beta, Gamma-bidentate Cr(III)ATPGammaS and Alpha, Beta-bidentate Cr(III) - ADPBetaS to be used as probes of the active sites of ATP-dependent enzymes. The enzymes which will be subjected to detailed study include yeast inorganic pyrophosphatase which catalyzes the hydrolysis of inorganic pyrophosphate and Tetrahymena pyriformis phosphoenolpyruvate phosphomutase which catalyzes the rearrangement of phosphoenolpyruvate to pyruvate phosphonic acid.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028688-07
Application #
3275956
Study Section
Biochemistry Study Section (BIO)
Project Start
1981-02-01
Project End
1989-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Maryland College Park
Department
Type
Earth Sciences/Resources
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742

  Publications

Latham, John A; Ji, Tianyang; Matthews, Kaila et al. (2017) Catalytic Mechanism of the Hotdog-Fold Thioesterase PA1618 Revealed by X-ray Structure Determination of a Substrate-Bound Oxygen Ester Analogue Complex. Chembiochem 18:1935-1943
Wu, Rui; Latham, John A; Chen, Danqi et al. (2014) Structure and catalysis in the Escherichia coli hotdog-fold thioesterase paralogs YdiI and YbdB. Biochemistry 53:4788-805
Latham, John A; Chen, Danqi; Allen, Karen N et al. (2014) Divergence of substrate specificity and function in the Escherichia coli hotdog-fold thioesterase paralogs YdiI and YbdB. Biochemistry 53:4775-87
Wang, Min; Song, Feng; Wu, Rui et al. (2013) Co-evolution of HAD phosphatase and hotdog-fold thioesterase domain function in the menaquinone-pathway fusion proteins BF1314 and PG1653. FEBS Lett 587:2851-9
Chen, Danqi; Latham, John; Zhao, Hong et al. (2012) Human brown fat inducible thioesterase variant 2 cellular localization and catalytic function. Biochemistry 51:6990-9
Zhuang, Zhihao; Latham, John; Song, Feng et al. (2012) Investigation of the catalytic mechanism of the hotdog-fold enzyme superfamily Pseudomonas sp. strain CBS3 4-hydroxybenzoyl-CoA thioesterase. Biochemistry 51:786-94
Song, Feng; Thoden, James B; Zhuang, Zhihao et al. (2012) The catalytic mechanism of the hotdog-fold enzyme superfamily 4-hydroxybenzoyl-CoA thioesterase from Arthrobacter sp. strain SU. Biochemistry 51:7000-16
Zhao, Hong; Lim, Kap; Choudry, Anthony et al. (2012) Correlation of structure and function in the human hotdog-fold enzyme hTHEM4. Biochemistry 51:6490-2
Kim, Alexander; Benning, Matthew M; OkLee, Sang et al. (2011) Divergence of chemical function in the alkaline phosphatase superfamily: structure and mechanism of the P-C bond cleaving enzyme phosphonoacetate hydrolase. Biochemistry 50:3481-94
Chen, Danqi; Wu, Rui; Bryan, Tyrel L et al. (2009) In vitro kinetic analysis of substrate specificity in enterobactin biosynthetic lower pathway enzymes provides insight into the biochemical function of the hot dog-fold thioesterase EntH. Biochemistry 48:511-3

Showing the most recent 10 out of 73 publications