Abstract:
:The human cytosolic sulfotransferases (SULTs) regulate hundreds, perhaps thousands, of small molecule metabolites and xenobiotics via transfer of a sulfuryl moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfate) to the hydroxyls and primary amines of the recipients. In liver, where it is abundant, SULT1A1 engages in modifying metabolites and neutralizing toxins. The specificity of 1A1 is the broadest of any SULT, and understanding its selectivity is fundamental to understanding its biology. Here, for the first time, we show that SULT1A1 substrates separate naturally into two classes: those whose affinities are either enhanced ∼20-fold (positive synergy) or unaffected (neutral synergy) by the presence of a saturating nucleotide. kcat for the positive-synergy substrates is shown to be ∼100-fold greater than that of neutral-synergy compounds; consequently, the catalytic efficiency (kcat/Km) is approximately 3 orders of magnitude greater for the positive-synergy species. All-atom dynamics modeling suggests a molecular mechanism for these observations in which the binding of only positive-synergy compounds causes two phenylalanine residues (F81 and 84) to reposition and "sandwich" the phenolic moiety of the substrates, thus enhancing substrate affinity and positioning the nucleophilic oxygen for attack. Molecular dynamics movies reveal that the neutral-synergy compounds "wander" about the active site, infrequently achieving a reactive position. In-depth analysis of select point mutants strongly supports the model and provides an intimate view of the interdependent catalytic functions of subsections of the active site.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Cook I,Wang T,Leyh TSdoi
10.1021/acs.biochem.5b00406subject
Has Abstractpub_date
2015-10-06 00:00:00pages
6114-22issue
39eissn
0006-2960issn
1520-4995journal_volume
54pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The thermodynamic quantities of the anti-dinitrophenyl antibody-hapten interaction are reported for rabbit, goat, and guinea pig antibodies. Rabbit and goat antibodies had similar exothermic enthalpy changes for their reaction with 2,4-dinitrophenyl-L-lysine (-13.9 and -14.8 kcal/mol, respectively). The enthalpy chang...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00694a032
更新日期:1975-11-18 00:00:00
abstract::To be fully active and participate in the metabolism of phosphorylated nucleotides, most nucleoside diphosphate kinases (NDPKs) have to assemble into stable hexamers. Here we studied the role played by six intersubunit salt bridges R80-D93 in the stability of NDPK from the pathogen Mycobacterium tuberculosis ( Mt). Mu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b01308
更新日期:2019-03-12 00:00:00
abstract::A highly active, large-scale preparation of ubiquinol:cytochrome c2 oxidoreductase (EC 1.10.2.2; cytochrome bc1 complex) has been obtained from Rhodobacter sphaeroides. The enzyme was solubilized from chromatophores by using dodecyl maltoside in the presence of glycerol and was purified by anion-exchange and gel filtr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00463a004
更新日期:1990-03-20 00:00:00
abstract::Early studies involving purine salvage in Salmonella typhimurium resulted in the isolation and identification of a mutant strain possessing a genetically modified hypoxanthine phosphoribosyl-transferase (HPRT) with enhanced substrate specificity for guanine [Benson, C. E., and Gots, J. S. (1975) J. Bacteriol. 121, 77-...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9720179
更新日期:1998-03-10 00:00:00
abstract::An in vitro system reconstituted with mouse liver polysome translation products was used to study the nature of polypeptide species imported into mitochondria from different mouse tissues such as liver, kidney, brain, and heart, as well as from Ehrlich ascites, Novikoff hepatoma, and Morris hepatoma 3924A tumor lines....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00348a041
更新日期:1985-12-31 00:00:00
abstract::The linkage between substrate and regulatory effector binding to separate sites on allosteric enzymes results in shifts in their sigmoidal kinetics to regulate metabolism. Control of branched chain amino acid biosynthesis in Escherichia coli occurs in part through shifts in the sigmoidal dependence of alpha-ketobutyra...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00029a016
更新日期:1995-07-25 00:00:00
abstract::The importance of the interdomain bridging interactions observed only in the R-state structure of Escherichia coli aspartate transcarbamylase between Glu-50 of the carbamoyl phosphate domain with both Arg-167 and Arg-234 of the aspartate domain has been investigated by using site-specific mutagenesis. Two mutant versi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00458a015
更新日期:1990-02-13 00:00:00
abstract::We have characterized by EPR the interaction of the Em,7 = -50 mV [4Fe-4S] cluster of Escherichia coli DMSO reductase (DmsABC) with a menaquinol (MQH2) binding site. Potentiometric titrations indicate that in DmsAB(C102S)C, the Em,7 = -50 mV [4Fe-4S] cluster is replaced by an Em,7 = +260 mV [3Fe-4S] cluster. The Q-poo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi951584y
更新日期:1996-03-12 00:00:00
abstract::A new strategy to form stable and sequence-specific triple helical DNA structures at mixed purine/pyrimidine sequences using a combination of four C-glycosides (TRIPsides) has been described [Li et al. (2003) J. Am. Chem. Soc. 125, 2084]. The partial realization of the approach is demonstrated by incorporating two of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035648d
更新日期:2004-02-17 00:00:00
abstract::Previous studies of the low molecular mass family 11 xylanase from Bacillus circulans show that the ionization state of the nucleophile (Glu78, pK(a) 4.6) and the acid/base catalyst (Glu172, pK(a) 6.7) gives rise to its pH-dependent activity profile. Inspection of the crystal structure of BCX reveals that Glu78 and Gl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:
更新日期:2001-08-28 00:00:00
abstract::A metabolite of vitamin D has been isolated in pure form from incubation of 25-hydroxyvitamin D3 with embryonic chick calvarial cells that had been grown on Cytodex 1 microcarrier beads. The isolation involved dichloromethane extraction of the cells and incubation medium, followed by Sephadex LH-20 column chromatograp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00274a012
更新日期:1983-03-01 00:00:00
abstract::Nuclear Overhauser effect (NOE) measurements are reported for the nonexchangeable base and ribose 1' proton resonances of CCGGAp, ACCGGp, and ACCGGUp. The results permit assignment of these resonances to particular nucleotides in the sequences. The NOE data rule out conformations containing syn glycosidic linkages and...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00271a005
更新日期:1983-01-18 00:00:00
abstract::Native ribonucleotide reductase from Escherichia coli exhibits a resonance-enhanced Raman mode at 1498 cm-1 that is characteristic of a tyrosyl radical. The Raman frequency as well as the absorption maximum at 410 nm identifies the radical as being in a deprotonated state. The B2 subunit of ribonucleotide reductase sh...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00430a074
更新日期:1989-02-21 00:00:00
abstract::We have examined the competitive binding of oxygen and carbon monoxide to the multisubunit hemocyanin of the tarantula Eurypelma californicum. Employment of high-precision thin-layer methods has enabled detailed characterization of the pure oxygen and pure carbon monoxide binding curves, as well as binding curves perf...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00418a036
更新日期:1988-09-06 00:00:00
abstract::To generate an effective immune response, class II major histocompatibility complex molecules (MHCII) must present a diverse array of peptide ligands for recognition by T lymphocytes. Peptide/MHCII complexes are stabilized by hydrophobic anchoring of peptide side chains to pockets in the MHCII protein and the formatio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048675s
更新日期:2005-04-19 00:00:00
abstract::Plasma high-density lipoprotein and apolipoprotein AI (apoAI) levels are suppressed by tumor necrosis factor alpha. To determine the molecular mechanisms responsible for the effect of TNF alpha on the apoAI promoter activity, HepG2 cells were exposed to both genetic and pharmacological modulators of TNF alpha-mediated...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0518040
更新日期:2006-02-21 00:00:00
abstract::Sensory rhodopsin I (SRI) is a seven-transmembrane helix retinylidene protein that mediates color-sensitive phototaxis responses through its bound transducer HtrI in the archaeon Halobacterium salinarum. Deprotonation of the Schiff base attachment site of the chromophore accompanies formation of the SRI signaling stat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991180w
更新日期:1999-10-05 00:00:00
abstract::The bacterial reaction center (RC) converts light into chemical energy through the reduction of an internal quinone molecule Q(B) to Q(B)H(2). In the native RC, proton transfer is coupled to electron transfer and is not rate-controlling. Consequently, proton transfer is not directly observable, and its rate was unknow...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi020419x
更新日期:2002-12-17 00:00:00
abstract::Cytidine deaminase from Escherichia coli contains 1 mol of tightly bound zinc per enzyme subunit (Yang, C., Carlow, D., Wolfenden, R., & Short, S.A. (1992) Biochemistry 31, 4168-4174). When the metal liganding residues Cys-129 and Cys-132 were replaced by Ala, and His-102 was replaced by Ala, Asn, or Gln, deaminase ac...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00187a012
更新日期:1994-05-31 00:00:00
abstract::Wideline 2H NMR spectroscopy was used to assess the conformational and orientational effects of N-acetylneuraminic acid (NeuAc) (sialic acid) as a component of a particular oligosaccharide chain at a bilayer membrane surface. For this purpose, three glycosphingolipids, sharing a neutral core tetrasaccharide and differ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952964m
更新日期:1996-04-16 00:00:00
abstract::Conformational factors that predicate selectivity for valine or isoleucine binding to IlvN leading to the regulation of aceto hydroxy acid synthase I (AHAS I) of Escherichia coli have been determined for the first time from high-resolution (1.9-2.43 Å) crystal structures of IlvN·Val and IlvN·Ile complexes. The valine ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00050
更新日期:2019-04-16 00:00:00
abstract::Traditional antibody generation, using either phage display or animal immunization, relies on purified antigens. Many membrane proteins, such as G protein-coupled receptors, solute carriers, or ion channels, are important drug targets but very challenging for the formation of antibodies due to the difficulty of protei...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.0c00730
更新日期:2020-11-10 00:00:00
abstract::The iron-chelating peptide vibriobactin of the pathogenic Vibrio cholerae is assembled by a four-subunit nonribosomal peptide synthetase complex, VibE, VibB, VibH, and VibF, using 2,3-dihydroxybenzoate and L-threonine as precursors to two 2,3-dihydroxyphenyl- (DHP-) methyloxazolinyl groups in amide linkage on a norspe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010937s
更新日期:2001-09-04 00:00:00
abstract::An alamethicin, secreted by the fungus Trichoderma viride and containing a glutamine at position 18 instead of the usual glutamic acid, has been uniformly labeled with 15N and purified by HPLC. The extent of 15N incorporation at individual backbone and side-chain sites was found to vary from 85% to 92%, as measured by...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00127a014
更新日期:1992-03-31 00:00:00
abstract::Terminase is an enzyme from bacteriophage lambda that is required for insertion of the viral genome into an empty pro-capsid. This enzyme is composed of the viral proteins gpNu1 (20.4 kDa) and gpA (73.3 kDa) in a holoenzyme complex. Current models for terminase assembly onto DNA suggest that gpNu1 binds to three repea...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981271d
更新日期:1999-01-05 00:00:00
abstract::Small molecule allostery modifies protein function but is not easily discovered. We introduce mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS), a method for identifying physiologically relevant, low-affinity metabolite-protein interactions using unmodified pr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi201313s
更新日期:2012-01-10 00:00:00
abstract::Bovine milk galactosyltransferase was examined by ESR and NMR proton relaxation measurements to determine the stoichiometry and nature of manganese and UDP-Gal substrate binding. The ESR and NMR data clearly showed the binding of two (Mn(II) per mol of enzyme in the ternary complex (enzyme-manganese-UDP-Gal). The affi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00546a017
更新日期:1980-03-04 00:00:00
abstract::The calcium pump [sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA)] transports Ca(2+) from the cytosol to the SR lumen at the expense of ATP hydrolysis and proton countertransport, thus playing a central role in Ca(2+) homeostasis and muscle contractility. Proton countertransport via deprotonation of transport site r...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00672
更新日期:2015-08-25 00:00:00
abstract::The thermotropic phase behavior of 10 mixed-chain phosphatidylcholines, in excess water, has been examined and compared with that of identical-chain C(16):C(16)PC by using high-resolution differential scanning calorimetry (DSC). The molecular weights (MW) of these 11 molecular species are the same, but their delta C/C...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00243a022
更新日期:1991-07-23 00:00:00
abstract::The contribution of ligand dynamics to CYP allosterism has not been considered in detail. On the basis of a previous study, we hypothesized that CYP2A6 and CYP2E1 accommodate multiple xylene ligands. As a result, the intramolecular ( k H/ k D) obs values observed for some xylene isomers are expected to be dependent on...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi702020y
更新日期:2008-03-04 00:00:00