Abstract:
:Tryptophan 2,3-dioxygenase (TDO) from Xanthomonas campestris is a highly specific heme-containing enzyme from a small family of homologous enzymes, which includes indoleamine 2,3-dioxygenase (IDO). The structure of wild type (WT TDO) in the catalytically active, ferrous (Fe (2+)) form and in complex with its substrate l-tryptophan ( l-Trp) was recently reported [Forouhar et al. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 473-478] and revealed that histidine 55 hydrogen bonds to l-Trp, precisely positioning it in the active site and implicating it as a possible active site base. In this study the substitution of the active site residue histidine 55 by alanine and serine (H55A and H55S) provides insight into the molecular mechanism used by the enzyme to control substrate binding. We report the crystal structure of the H55A and H55S mutant forms at 2.15 and 1.90 A resolution, respectively, in binary complexes with l-Trp. These structural data, in conjunction with potentiometric and kinetic studies on both mutants, reveal that histidine 55 is not essential for turnover but greatly disfavors the mechanistically unproductive binding of l-Trp to the oxidized enzyme allowing control of catalysis. This is demonstrated by the difference in the K d values for l-Trp binding to the two oxidation states of wild-type TDO (3.8 mM oxidized, 4.1 microM reduced), H55A TDO (11.8 microM oxidized, 3.7 microM reduced), and H55S TDO (18.4 microM oxidized, 5.3 microM reduced).
journal_name
Biochemistryjournal_title
Biochemistryauthors
Thackray SJ,Bruckmann C,Anderson JL,Campbell LP,Xiao R,Zhao L,Mowat CG,Forouhar F,Tong L,Chapman SKdoi
10.1021/bi801202asubject
Has Abstractpub_date
2008-10-07 00:00:00pages
10677-84issue
40eissn
0006-2960issn
1520-4995journal_volume
47pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Bleeding, the most serious complication of thrombolytic therapy with tissue-type plasminogen activator (t-PA), is thought to result from lysis of fibrin in hemostatic plugs and from the systemic lytic state caused by unopposed plasmin. One mechanism by which systemic plasmin can impair hemostasis is by partially degra...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0525730
更新日期:2006-04-04 00:00:00
abstract::Excitation energy transfer studies were carried out to determine the distance between the adenosinetriphosphatase (ATPase) site and a unique "fast-reacting" sulfhydryl (referred to as SH1) in myosin subfragment 1. The fluorescent moiety of the probe N-(iodoacetyl)-N'-(5-sulfo-1-naphthyl)ethylene-diamine was used as th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00520a035
更新日期:1981-08-18 00:00:00
abstract::Gram-negative bacteria, such as Escherichia coli, utilize efflux resistance systems in order to expel toxins from their cells. Heavy-metal resistance is mediated by resistance nodulation cell division (RND)-based efflux pumps composed of a tripartite complex that includes an RND-transporter, an outer-membrane factor (...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi300596a
更新日期:2012-08-28 00:00:00
abstract::Resonances of the histidine region of human carbonic anhydrase B have been studied by proton magnetic resonance spectroscopy in the presence of seven sulfonamide inhibitors. Results of difference spectroscopy and observation of the C-2 resonance of an additional titratable histidine in some of these spectra suggest a ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00675a007
更新日期:1975-02-25 00:00:00
abstract::The crystal structure of ferredoxin-NADP+ reductase (FNR) suggests that Ser96 is directly involved in hydride transfer between the isoalloxazine moiety of FAD and the nicotinamide ring of NADP(H). To probe its role, Ser96 has been mutated to valine (S96V) and glycine (S96G). These mutations primarily affected the inte...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00026a019
更新日期:1995-07-04 00:00:00
abstract::Furamidine and related diamidines represent a promising series of drugs active against widespread parasites, in particular the Pneumocystic carinii pathogen. In this series, the phenylfuranbenzimidazole diamidine derivative DB293 was recently identified as the first unfused aromatic dication capable of forming stacked...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0108453
更新日期:2001-08-21 00:00:00
abstract::Kinetic and structural changes in recombinant human aldose reductase (AR) due to modification by S-nitrosoglutathione (GSNO) were investigated. Incubation of the enzyme with 10-50 microM GSNO led to a time- and concentration-dependent inactivation of the enzyme, with a second-order rate constant of 0.087 +/- 0.009 M-1...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9714722
更新日期:1997-12-16 00:00:00
abstract::A series of truncated forms of His(6)-tagged gp91phox were expressed, solubilized, and purified in the presence of 30 microM FAD. The truncated gp91phox with the longest sequence in the C-terminal region (221-570) (gp91C) showed the highest activity (turnover rate, 0.92) for NADPH diaphorase in the presence of either ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0400249
更新日期:2004-07-27 00:00:00
abstract::Raman spectroscopy was used to study the phase behavior of several semisynthetic species of the acidic glycosphingolipid cerebroside sulfate (CBS) which occur in myelin. The C-H stretching mode region at 2800-3100 cm-1 of C18:0-CBS, C24:0-CBS, and C26:0-CBS, and the alpha-hydroxy fatty acid species C18:0h-CBS, was stu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00121a041
更新日期:1992-02-18 00:00:00
abstract::Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messenger...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0508845
更新日期:2005-08-23 00:00:00
abstract::The E-domain of staphylococcal protein A is one of five homologous IgG-binding domains designated E, D, A, B, and C that comprise the extracellular portion of protein A. The E-domain binds tightly to Fc fragments of IgG and binds certain Fv fragments with micromolar affinity. To explore further the structural features...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi961409x
更新日期:1996-12-03 00:00:00
abstract::We have investigated, both experimentally and theoretically, the efflux of carboxyfluorescein (a self-quenching fluorescent dye) from vesicles of different sizes and lipid species (POPC, DOPC) after having added the bee venom peptide melittin. This comprises quantitative analyses regarding the extent of lipid-associat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi971009p
更新日期:1998-02-24 00:00:00
abstract::The understanding of interactions between small molecules and DNA is crucial to design new anticancer drugs targeted to DNA. Methylene blue (MB) is a phenothiazinium dye that has shown promising results in photodynamic therapy treatment. The noncovalent binding of methylene blue to DNA was experimentally and theoretic...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi500068z
更新日期:2014-04-15 00:00:00
abstract::Actin-depolymerizing factor (ADF)/cofilin enhances the turnover of actin filaments by two separable activities: filament severing and pointed-end depolymerization. Multicellular organisms express multiple ADF/cofilin isoforms in a tissue-specific manner, and the vertebrate proteins are grouped into ADFs and cofilins o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi050933d
更新日期:2005-11-01 00:00:00
abstract::The structures of ternary complexes of human inositol monophosphatase with inhibitory Gd3+ and either D- or L-myo-inositol 1-phosphate have been determined to 2.2-2.3 A resolution using X-ray crystallography. Substrate and metal are bound identically in each active site of the phosphatase dimer. The substrate is prese...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00198a011
更新日期:1994-08-16 00:00:00
abstract::Basic peptides from the carboxy terminus of the human immunodeficiency virus type 1 (HIV-1) Tat protein bind to the stem-loop region of TAR RNA, spanning a trinucleotide bulge, with high affinity and moderate specificity. Previous studies have demonstrated that TAR RNA contains a specific arginine binding pocket. A se...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00027a041
更新日期:1995-07-11 00:00:00
abstract::In bacteria, two-component systems act as signaling systems to respond to environmental stimuli. Two-component systems generally consist of a sensor histidine kinase and a response regulator, which work together through histidyl-aspartyl phosphorelay to result in gene regulation. One of the two-component systems in Es...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00707
更新日期:2016-09-20 00:00:00
abstract::Some key chloroplast enzymes are activated by light via a ferredoxin-thioredoxin reduction system which reduces disulfide bridges in the enzymes. We describe for the first time the structural basis for the redox activation of a chloroplast enzyme, the NADP-dependent malate dehydrogenase (MDH) from Sorghum vulgare whos...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982876c
更新日期:1999-04-06 00:00:00
abstract::Binding of the nonhydrolyzable ATP analogue 5'-adenylyl-beta, gamma-imidodiphosphate (ADPNP) to Escherichia coli DNA gyrase can lead to a limited noncatalytic supercoiling of DNA. Here we examine the efficiency of coupling between ADPNP binding and the change in linking number either of positively or negatively superc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952433y
更新日期:1996-02-06 00:00:00
abstract::Depletion of functional Ca2+ from photosystem (PS) II membranes impairs O2 evolution. Redox properties of the Mn cluster as probed by thermoluminescence were modified differently in Ca(2+)-depleted PSII depending on the procedure for Ca2+ extraction. Ca2+ depletion by low-pH treatment gave rise to an abnormally modifi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00148a028
更新日期:1992-08-25 00:00:00
abstract::The protease activity of hepatitis C virus nonstructural protein 3 (NS3) is essential for viral replication. ITMN-191, a macrocyclic inhibitor of the NS3 protease active site, promotes rapid, multilog viral load reductions in chronic HCV patients. Here, ITMN-191 is shown to be a potent inhibitor of NS3 with a two-step...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900038p
更新日期:2009-03-24 00:00:00
abstract::Membranes derived from free floating granulosa cells in porcine ovarian follicular fluid were used as a starting material for structural characterization of both LH/hCG and FSH receptors. The receptors were highly hormone-specific and showed single classes of high-affinity binding sites (Kd = 19-74 pM). Their molecula...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00467a022
更新日期:1990-04-17 00:00:00
abstract::A method is described for using very high specific activity [3H]poly(deoxythymidylate) [[3H]poly(dT)] to detect, size, and quantiate subnanogram amounts of nonradioactive polyadenylated RNA. Short (approximately 100 nucleotides long) [3H]poly(dT) is hybridized to the poly(adenylate) [poly(A)] tracts in polyadenylated ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00557a022
更新日期:1980-08-05 00:00:00
abstract::A general kinetic model for catalysis by interfacial enzymes is developed. It couples the Michaelis-Menten catalytic turnover cycle at the interface with that in the aqueous phase through the distribution equilibria between the interface and the surrounding aqueous phase. Analysis under two limiting conditions fully d...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970855x
更新日期:1997-11-25 00:00:00
abstract::Peptides corresponding to portions of curaremimetic neurotoxin loop 2 and to a structurally similar segment of rabies virus glycoprotein were synthetically modified in order to gain information on structure-function relationships of neurotoxin loop 2 interactions with the acetylcholine receptor. Binding of synthetic p...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00109a020
更新日期:1991-11-12 00:00:00
abstract::5-Hydroxy-1,2-naphthalenedicarboxylic anhydride is closely related to its precursor dibasic acid which is a metabolite of the carcinogenic polynuclear hydrocarbon dibenz[a,h]anthracene. The anhydride inhibited respiration of coupled mitochondria. This inhibition was relieved by 2,4-dinitrophenol. Several mitochondrial...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00695a022
更新日期:1975-12-02 00:00:00
abstract::In this work, we show that adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) is a substrate for yeast inorganic pyrophosphatase (PPase) (EC 3.6.1.1) and further, using chirally labeled [gamma-17O,18O]ATP gamma S, that enzyme-catalyzed hydrolysis to produce chiral inorganic thio[17O,18O]phosphate proceeds with inversio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00300a002
更新日期:1984-02-28 00:00:00
abstract::Four mechanisms for the allosteric regulation of the calcium and magnesium ion activated adenosinetriphosphatase (Ca,Mg-ATPase) of sarcoplasmic reticulum were examined. Negative cooperativity in substrate binding was not supported by 3H-labeled 5'-adenylyl methylenediphosphate (AMPPCP) binding, which was best fit by a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00341a049
更新日期:1985-09-24 00:00:00
abstract::MRP1 (or ABCC1) is an ABC membrane protein that transports a wide range of natural products as well as glutathione (GSH)-, glucuronate-, and sulfate-conjugated metabolites. In addition, free GSH is required for MRP1 to transport several chemotherapeutic drugs. However, the mechanisms regulating the influence of GSH on...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0268807
更新日期:2003-03-25 00:00:00
abstract::The proton nuclear magnetic resonance spectrum of human adult deoxyhemoglobin in D2O in the region from 6 to 20 ppm downfield from the proton resonance of residual water shows a number of hyperfine shifted proton resonances that are due to groups on or near the alpha and beta hemes. The sensitivity of these resonances...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00590a031
更新日期:1979-11-13 00:00:00