Elsliger MA

References (5)

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

Title : Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A\/protective protein gene - Richard_1998_Hum.Mutat_11_461
Author(s) : Richard C , Tranchemontagne J , Elsliger MA , Mitchell GA , Potier M , Pshezhetsky AV
Ref : Hum Mutat , 11 :461 , 1998
Abstract : Galactosialidosis is a recessively inherited lysosomal storage disease characterized by the combined deficiency of neuraminidase and beta-galactosidase secondary to the genetic deficiency of cathepsin A/protective protein. In lysosomes, cathepsin A forms a high-molecular-weight complex with beta-galactosidase and neuraminidase that protects these enzymes against intralysosomal proteolysis. In a patient affected with late infantile form of galactosialidosis, we found two new cathepsin A mutations, a two-nucleotide deletion, c517delTT and an intronic mutation, IVS8+9C-->G resulting in abnormal splicing and a five-nucleotide insertion in the cathepsin A cDNA. Both mutations cause frameshifts and result in the synthesis of truncated cathepsin A proteins, which, as suggested by structural modeling, are incapable of dimerization, complex formation, and catalysis. However, enzymatic assays, gel-filtration, and Western blot analysis of the patient's cultured skin fibroblast extracts showed the presence of a small amount of normal-size, catalytically active cathepsin A and cathepsin A-beta-galactosidase 680 kDa complex, suggesting that a low amount of cathepsin A mRNA is spliced normally and produces the wild-type protein. This may contribute to the relatively mild phenotype of the patient and illustrates the importance of critically comparing molecular results with clinical and biochemical phenotypes.
ESTHER : Richard_1998_Hum.Mutat_11_461
PubMedSearch : Richard_1998_Hum.Mutat_11_461
PubMedID: 9603439
Gene_locus related to this paper: human-CTSA

Title : Homologous modeling of the lysosomal protective protein\/carboxypeptidase L: structural and functional implications of mutations identified in galactosialidosis patients - Elsliger_1994_Proteins_18_81
Author(s) : Elsliger MA , Potier M
Ref : Proteins , 18 :81 , 1994
Abstract : The deficiency of the lysosomal protective protein/carboxypeptidase L (CARB L) causes the lysosomal storage disorder, galactosialidosis, characterized by neuraminidase and beta-galactosidase deficiencies in patients' cells. The three enzymes form a complex inside the lysosome, and the neuraminidase and beta-galactosidase deficiencies are secondary to CARB L deficiency. Sequence similarity and common enzymological properties suggest that the protomeric tertiary structure of CARB L is conserved within a family of serine carboxypeptidases which includes the yeast carboxypeptidase Y, killer expression I gene product and several plant carboxypeptidases. We used this homology to build a model of the CARB L structure based on the recently published X-ray atomic coordinates of the wheat carboxypeptidase II (CPDW-II) which shares 32% primary structure identity with CARB L. Small insertions and deletions were accommodated into the model structure by energy minimization using the DREIDING II force field. The C alpha atomic coordinates of the final CARB L model have a RMS shift of 1.01 A compared to the corresponding conserved residues in the CPDW-II template structure. The correct orientation of the homologous catalytic triad residues Ser150, His429 and Asp392, the potential energy calculations and the distribution of hydrophobic and hydrophillic residues in the structure all support the validity of the CARB L model. Most missense mutations identified in galactosialidosis patients were located in secondary structural elements except for the Tyr211-->Asn mutation which is in a loop. The other mutant residues have their side chains deeply buried in the central beta-sheet of the model structure except for the Phe412-->Val mutation which is located in the dimer interface. The predicted effects of specific mutations on CARB L structural stability correlates well with recently published transient expression studies of mutant CARB L (Shimmoto, M. et al., J. Clin. Invest., 91:2393-2399, 1993).
ESTHER : Elsliger_1994_Proteins_18_81
PubMedSearch : Elsliger_1994_Proteins_18_81
PubMedID: 8146124