Russell A

References (3)

Title : Fluorogenic structure activity library pinpoints molecular variations in substrate specificity of structurally homologous esterases - White_2018_J.Biol.Chem_293_13851
Author(s) : White A , Koelper A , Russell A , Larsen EM , Kim C , Lavis LD , Hoops GC , Johnson RJ
Ref : Journal of Biological Chemistry , 293 :13851 , 2018
Abstract : Cellular esterases catalyze many essential biological functions by performing hydrolysis reactions on diverse substrates. The promiscuity of esterases complicates assignment of their substrate preferences and biological functions. To identify universal factors controlling esterase substrate recognition, we designed a 32-member structure-activity relationship (SAR) library of fluorogenic ester substrates and used this library to systematically interrogate esterase preference for chain length, branching patterns, and polarity to differentiate common classes of esterase substrates. Two structurally homologous bacterial esterases were screened against this library, refining their previously broad overlapping substrate specificity. Vibrio cholerae esterase ybfF displayed a preference for gamma-position thioethers and ethers, whereas Rv0045c from Mycobacterium tuberculosis displayed a preference for branched substrates with and without thioethers. We determined that this substrate differentiation was partially controlled by individual substrate selectivity residues Tyr-119 in ybfF and His-187 in Rv0045c; reciprocal substitution of these residues shifted each esterase's substrate preference. This work demonstrates that the selectivity of esterases is tuned based on transition state stabilization, identifies thioethers as an underutilized functional group for esterase substrates, and provides a rapid method for differentiating structural isozymes. This SAR library could have multifaceted future applications, including in vivo imaging, biocatalyst screening, molecular fingerprinting, and inhibitor design.
ESTHER : White_2018_J.Biol.Chem_293_13851
PubMedSearch : White_2018_J.Biol.Chem_293_13851
PubMedID: 30006352
Gene_locus related to this paper: myctu-RV0045C , vibch-VC2097

Title : Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla - Mahowald_2009_Proc.Natl.Acad.Sci.U.S.A_106_5859
Author(s) : Mahowald MA , Rey FE , Seedorf H , Turnbaugh PJ , Fulton RS , Wollam A , Shah N , Wang C , Magrini V , Wilson RK , Cantarel BL , Coutinho PM , Henrissat B , Crock LW , Russell A , VerBerkmoes NC , Hettich RL , Gordon JI
Ref : Proc Natl Acad Sci U S A , 106 :5859 , 2009
Abstract : The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial-microbial and microbial-host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.
ESTHER : Mahowald_2009_Proc.Natl.Acad.Sci.U.S.A_106_5859
PubMedSearch : Mahowald_2009_Proc.Natl.Acad.Sci.U.S.A_106_5859
PubMedID: 19321416
Gene_locus related to this paper: eube2-c4z2j4 , eube2-c4z5d5 , eube2-c4z6k4 , eube2-c4z179 , eube2-c4z180 , eubr3-c4z8a6 , eubr3-c4zfm2 , eubr3-c4zhp3 , eubr3-c4zf28

Title : Long-Term Effects of AF64A on Learning and Memory Processes in the Rat -
Author(s) : Walsh TJ , DeHaven DL , Russell A , Hanin I
Ref : Advances in Behavioral Biology , 30 :1127 , 1986