Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The project involves an unusual protein disulfide isomerase, GILT, that works at acidic conditions in the lysosome. It is involved in mhc class II maturation and also plays a key role in the hi-jacking of cells by pathogens. We have selenomethionine substituted crystals of two differenet mutants with which we would like to use for phasing. These crystals can diffract to better than 3A on our home source and we expect better resolution at a synchrotron source. We have several pre-screened crystals and ~20 that we would also like to screen/collect on.The structural studies on GILT will help us to elucidate the enzymatic mechanism of the protein, and how it works at the acidic pH of the lysosome. Furthermore, this work will lay the basis to understand its involvement in pathogenic processes on a molecular level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR012408-15
Application #
8363345
Study Section
Special Emphasis Panel (ZRG1-BCMB-R (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
15
Fiscal Year
2011
Total Cost
$2,111
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
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

Showing the most recent 10 out of 167 publications