Lesley SA

References (4)

Title : Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis - Park_2015_J.Chem.Inf.Model_55_1914
Author(s) : Park IH , Venable JD , Steckler C , Cellitti SE , Lesley SA , Spraggon G , Brock A
Ref : J Chem Inf Model , 55 :1914 , 2015
Abstract : Hydrogen exchange (HX) studies have provided critical insight into our understanding of protein folding, structure, and dynamics. More recently, hydrogen exchange mass spectrometry (HX-MS) has become a widely applicable tool for HX studies. The interpretation of the wealth of data generated by HX-MS experiments as well as other HX methods would greatly benefit from the availability of exchange predictions derived from structures or models for comparison with experiment. Most reported computational HX modeling studies have employed solvent-accessible-surface-area based metrics in attempts to interpret HX data on the basis of structures or models. In this study, a computational HX-MS prediction method based on classification of the amide hydrogen bonding modes mimicking the local unfolding model is demonstrated. Analysis of the NH bonding configurations from molecular dynamics (MD) simulation snapshots is used to determine partitioning over bonded and nonbonded NH states and is directly mapped into a protection factor (PF) using a logistics growth function. Predicted PFs are then used for calculating deuteration values of peptides and compared with experimental data. Hydrogen exchange MS data for fatty acid synthase thioesterase (FAS-TE) collected for a range of pHs and temperatures was used for detailed evaluation of the approach. High correlation between prediction and experiment for observable fragment peptides is observed in the FAS-TE and additional benchmarking systems that included various apo/holo proteins for which literature data were available. In addition, it is shown that HX modeling can improve experimental resolution through decomposition of in-exchange curves into rate classes, which correlate with prediction from MD. Successful rate class decompositions provide further evidence that the presented approach captures the underlying physical processes correctly at the single residue level. This assessment is further strengthened in a comparison of residue resolved protection factor predictions for staphylococcal nuclease with NMR data, which was also used to compare prediction performance with other algorithms described in the literature. The demonstrated transferable and scalable MD based HX prediction approach adds significantly to the available tools for HX-MS data interpretation based on available structures and models.
ESTHER : Park_2015_J.Chem.Inf.Model_55_1914
PubMedSearch : Park_2015_J.Chem.Inf.Model_55_1914
PubMedID: 26241692
Gene_locus related to this paper: human-FASN

Title : Functional and structural characterization of a thermostable acetyl esterase from Thermotoga maritima - Levisson_2012_Proteins_80_1545
Author(s) : Levisson M , Han GW , Deller MC , Xu Q , Biely P , Hendriks S , Ten Eyck LF , Flensburg C , Roversi P , Miller MD , McMullan D , von Delft F , Kreusch A , Deacon AM , Van der Oost J , Lesley SA , Elsliger MA , Kengen SW , Wilson IA
Ref : Proteins , 80 :1545 , 2012
Abstract : TM0077 from Thermotoga maritima is a member of the carbohydrate esterase family 7 and is active on a variety of acetylated compounds, including cephalosporin C. TM0077 esterase activity is confined to short-chain acyl esters (C2-C3), and is optimal around 100degC and pH 7.5. The positional specificity of TM0077 was investigated using 4-nitrophenyl--D-xylopyranoside monoacetates as substrates in a -xylosidase-coupled assay. TM0077 hydrolyzes acetate at positions 2, 3, and 4 with equal efficiency. No activity was detected on xylan or acetylated xylan, which implies that TM0077 is an acetyl esterase and not an acetyl xylan esterase as currently annotated. Selenomethionine-substituted and native structures of TM0077 were determined at 2.1 and 2.5 resolution, respectively, revealing a classicalpha/beta-hydrolase fold. TM0077 assembles into a doughnut-shaped hexamer with small tunnels on either side leading to an inner cavity, which contains the six catalytic centers. Structures of TM0077 with covalently bound phenylmethylsulfonyl fluoride and paraoxon were determined to 2.4 and 2.1 , respectively, and confirmed that both inhibitors bind covalently to the catalytic serine (Ser188). Upon binding of inhibitor, the catalytic serine adopts an altered conformation, as observed in other esterase and lipases, and supports a previously proposed catalytic mechanism in which Ser hydroxyl rotation prevents reversal of the reaction and allows access of a water molecule for completion of the reaction.
ESTHER : Levisson_2012_Proteins_80_1545
PubMedSearch : Levisson_2012_Proteins_80_1545
PubMedID: 22411095
Gene_locus related to this paper: thema-TM0077

Title : Crystal structure of homoserine O-succinyltransferase from Bacillus cereus at 2.4 A resolution -
Author(s) : Zubieta C , Krishna SS , McMullan D , Miller MD , Abdubek P , Agarwalla S , Ambing E , Astakhova T , Axelrod HL , Carlton D , Chiu HJ , Clayton T , Deller M , DiDonato M , Duan L , Elsliger MA , Grzechnik SK , Hale J , Hampton E , Han GW , Haugen J , Jaroszewski L , Jin KK , Klock HE , Knuth MW , Koesema E , Kumar A , Marciano D , Morse AT , Nigoghossian E , Oommachen S , Reyes R , Rife CL , van den Bedem H , Weekes D , White A , Xu Q , Hodgson KO , Wooley J , Deacon AM , Godzik A , Lesley SA , Wilson IA
Ref : Proteins , 68 :999 , 2007
PubMedID: 17546672
Gene_locus related to this paper: bacce-BC4730

Title : Crystal structure of an alpha\/beta serine hydrolase (YDR428C) from Saccharomyces cerevisiae at 1.85 A resolution -
Author(s) : Arndt JW , Schwarzenbacher R , Page R , Abdubek P , Ambing E , Biorac T , Canaves JM , Chiu HJ , Dai X , Deacon AM , DiDonato M , Elsliger MA , Godzik A , Grittini C , Grzechnik SK , Hale J , Hampton E , Han GW , Haugen J , Hornsby M , Klock HE , Koesema E , Kreusch A , Kuhn P , Jaroszewski L , Lesley SA , Levin I , McMullan D , McPhillips TM , Miller MD , Morse A , Moy K , Nigoghossian E , Ouyang J , Peti WS , Quijano K , Reyes R , Sims E , Spraggon G , Stevens RC , van den Bedem H , Velasquez J , Vincent J , von Delft F , Wang X , West B , White A , Wolf G , Xu Q , Zagnitko O , Hodgson KO , Wooley J , Wilson IA
Ref : Proteins , 58 :755 , 2005
PubMedID: 15624212
Gene_locus related to this paper: yeast-YDR428C