Abstract

This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Lipopolysaccharide (LPS) is a major component of the Gram-negative bacterial cell wall. LPS is comprised of three components: lipid A, core polysaccharide (Kdo and one or more heptose residues), and polysaccharide side chains. LPS biosynthesis that is halted prior to heptose addition results in a deep-rough phenotype and membrane permeability to antibiotics is increased. For this reason, the heptose biosynthetic pathway has been marked as a potential drug target. Our goal is to determine the mechanism of GmhA, an isomerase that catalyzes the first committed step of ADP-L-glycero- x-manno-heptose biosynthesis as well as GmhB and HldE which are also key players in LPS biosynthesis. Determination of the enzymatic mechanisms used by these proteins will aid in the rational design of inhibitors of GmhA, GmhB and HldE as a means to combat Gram negative infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR012408-12
Application #
7726202
Study Section
Special Emphasis Panel (ZRG1-BCMB-R (40))
Project Start
2008-09-18
Project End
2009-06-30
Budget Start
2008-09-18
Budget End
2009-06-30
Support Year
12
Fiscal Year
2008
Total Cost
$13,418
Indirect Cost

  Institution

Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973

  Publications

Sui, Xuewu; Farquhar, Erik R; Hill, Hannah E et al. (2018) Preparation and characterization of metal-substituted carotenoid cleavage oxygenases. J Biol Inorg Chem 23:887-901
Jacques, Benoit; Coinçon, Mathieu; Sygusch, Jurgen (2018) Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6-bisphosphate aldolases. J Biol Chem 293:7737-7753
Fuller, Franklin D; Gul, Sheraz; Chatterjee, Ruchira et al. (2017) Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers. Nat Methods 14:443-449
Wangkanont, Kittikhun; Winton, Valerie J; Forest, Katrina T et al. (2017) Conformational Control of UDP-Galactopyranose Mutase Inhibition. Biochemistry 56:3983-3992
VanderLinden, Ryan T; Hemmis, Casey W; Yao, Tingting et al. (2017) Structure and energetics of pairwise interactions between proteasome subunits RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism. J Biol Chem 292:9493-9504
Song, Lingshuang; Yang, Lin; Meng, Jie et al. (2017) Thermodynamics of Hydrophobic Amino Acids in Solution: A Combined Experimental-Computational Study. J Phys Chem Lett 8:347-351
Orlova, Natalia; Gerding, Matthew; Ivashkiv, Olha et al. (2017) The replication initiator of the cholera pathogen's second chromosome shows structural similarity to plasmid initiators. Nucleic Acids Res 45:3724-3737
Firestone, Ross S; Cameron, Scott A; Karp, Jerome M et al. (2017) Heat Capacity Changes for Transition-State Analogue Binding and Catalysis with Human 5'-Methylthioadenosine Phosphorylase. ACS Chem Biol 12:464-473
Young, Iris D; Ibrahim, Mohamed; Chatterjee, Ruchira et al. (2016) Structure of photosystem II and substrate binding at room temperature. Nature 540:453-457
Buensuceso, Ryan N C; Nguyen, Ylan; Zhang, Kun et al. (2016) The Conserved Tetratricopeptide Repeat-Containing C-Terminal Domain of Pseudomonas aeruginosa FimV Is Required for Its Cyclic AMP-Dependent and -Independent Functions. J Bacteriol 198:2263-74

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