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.
We aim to characterize the three-dimensional structure of Escherichia coli spermidine synthase (SpeE) and to carry out functional studies for this enzyme. SpeE catalyzes the synthesis of spermidine, which is a known polyamine. Polyamines such as putrescine, spermidine and spermine, are polycationic and linear aliphatic compounds present in significant amount in living organisms. They neutralize intracellular polyanions, especially DNA and therefore providing stability for DNA molecules in the cell. They are also known to be important factors of DNA, RNA and protein synthesis. Bacteria growth is stimulated by polyamines. Polyamines accumulation has also been observed in cancerous tissues. Inhibition of polyamine biosynthesis and depletion of intracellular polyamine content has become a potential therapeutic method for the treatment of bacterial infection and cancer. Structure and functional characterization of SpeE is crucial as these studies will facilitate the rational design of such potential drugs that inhibit the enzyme.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR012408-12
Application #
7726222
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
$15,875
Indirect Cost
Name
Brookhaven National Laboratory
Department
Type
DUNS #
027579460
City
Upton
State
NY
Country
United States
Zip Code
11973
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
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
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
Tajima, Nami; Karakas, Erkan; Grant, Timothy et al. (2016) Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Nature 534:63-8
Ericson, Daniel L; Yin, Xingyu; Scalia, Alexander et al. (2016) Acoustic Methods to Monitor Protein Crystallization and to Detect Protein Crystals in Suspensions of Agarose and Lipidic Cubic Phase. J Lab Autom 21:107-14

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