The structure of Escherichia coli cytosine deaminase.

Abstract:

:Cytosine deaminase (CD) catalyzes the deamination of cytosine, producing uracil. This enzyme is present in prokaryotes and fungi (but not multicellular eukaryotes) and is an important member of the pyrimidine salvage pathway in those organisms. The same enzyme also catalyzes the conversion of 5-fluorocytosine to 5-fluorouracil; this activity allows the formation of a cytotoxic chemotherapeutic agent from a non-cytotoxic precursor. The enzyme is of widespread interest both for antimicrobial drug design and for gene therapy applications against tumors. The structure of Escherichia coli CD has been determined in the presence and absence of a bound mechanism-based inhibitor. The enzyme forms an (alphabeta)(8) barrel structure with structural similarity to adenosine deaminase, a relationship that is undetectable at the sequence level, and no similarity to bacterial cytidine deaminase. The enzyme is packed into a hexameric assembly stabilized by a unique domain-swapping interaction between enzyme subunits. The active site is located in the mouth of the enzyme barrel and contains a bound iron ion that coordinates a hydroxyl nucleophile. Substrate binding involves a significant conformational change that sequesters the reaction complex from solvent.

journal_name

J Mol Biol

authors

Ireton GC,McDermott G,Black ME,Stoddard BL

doi

10.1006/jmbi.2001.5277

keywords:

subject

Has Abstract

pub_date

2002-01-25 00:00:00

pages

687-97

issue

4

eissn

0022-2836

issn

1089-8638

pii

S0022283601952775

journal_volume

315

pub_type

杂志文章
  • Testing for intron function in the essential Saccharomyces cerevisiae tRNA(SerUCG) gene.

    abstract::The gene sup61+, which codes for the essential Saccharomyces cerevisiae tRNA(SerUCG), is the only single-copy tRNA gene in this organism know to contain an intron. To assess the role of this intron in tRNA gene expression, an intron-deleted sup61+ gene was constructed in vitro and introduced into the yeast genome. Iso...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(88)90295-1

    authors: Ho CK,Abelson J

    更新日期:1988-08-05 00:00:00

  • The 5' ends of Escherichia coli lac mRNA.

    abstract::We identified the predominant 5' ends of an mRNA in Escherichia coli to the exact nucleotides. There are four such ends of lac mRNA in fully induced cells. About 70% of the molecules have the reported major in vitro end, A-A-U-U-G (at +1), which is located 38 nucleotides before the A-U-G translation start. Another 15%...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(85)90342-0

    authors: Cannistraro VJ,Kennell D

    更新日期:1985-03-20 00:00:00

  • Structural reorganization of alpha-synuclein at low pH observed by NMR and REMD simulations.

    abstract::alpha-Synuclein is an intrinsically disordered protein that appears in aggregated forms in the brains of patients with Parkinson's disease. The conversion from monomer to aggregate is complex, and aggregation rates are sensitive to changes in amino acid sequence and environmental conditions. It has previously been obs...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2009.06.063

    authors: Wu KP,Weinstock DS,Narayanan C,Levy RM,Baum J

    更新日期:2009-08-28 00:00:00

  • Regulatory sequences in sigma 54 localise near the start of DNA melting.

    abstract::Transcription initiation by the enhancer-dependent sigma(54) RNA polymerase holoenzyme is positively regulated after promoter binding. The promoter DNA melting process is subject to activation by an enhancer-bound activator protein with nucleoside triphosphate hydrolysis activity. Tethered iron chelate probes attached...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.4393

    authors: Wigneshweraraj SR,Chaney MK,Ishihama A,Buck M

    更新日期:2001-03-02 00:00:00

  • Evolution of function in protein superfamilies, from a structural perspective.

    abstract::The recent growth in protein databases has revealed the functional diversity of many protein superfamilies. We have assessed the functional variation of homologous enzyme superfamilies containing two or more enzymes, as defined by the CATH protein structure classification, by way of the Enzyme Commission (EC) scheme. ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2001.4513

    authors: Todd AE,Orengo CA,Thornton JM

    更新日期:2001-04-06 00:00:00

  • Homotropic effects in aspartate transcarbamoylase. What happens when the enzyme binds a single molecule of the bisubstrate analog N-phosphonacetyl-L-aspartate?

    abstract::The active sites of aspartate transcarbamoylase from Escherichia coli were titrated by measuring the decrease in the enzyme-catalyzed arsenolysis of N-carbamoyl-L-aspartate caused by the addition of the tight-binding inhibitor, N-phosphonacetyl-L-aspartate. Because the enzyme is a poor catalyst for this non-physiologi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(85)90267-0

    authors: Foote J,Schachman HK

    更新日期:1985-11-05 00:00:00

  • One is Nothing without the Other: Theoretical and Empirical Analysis of Cell Growth and Cell Cycle Progression.

    abstract::Small, fast-growing bacteria make ideal subjects for genetic and quantitative analysis alike. Long the darling of theoreticians, efforts to understand the relationship between cell growth and cell cycle progression in bacterial systems have been propelled by modelers and empiricist in equal measure. Taking a historica...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jmb.2019.04.004

    authors: Levin PA,Taheri-Araghi S

    更新日期:2019-05-17 00:00:00

  • Bacterial repression loops require enhanced DNA flexibility.

    abstract::The Escherichia coli lac operon provides a classic paradigm for understanding regulation of gene transcription. It is now appreciated that lac promoter repression involves cooperative binding of the bidentate lac repressor tetramer to pairs of lac operators via DNA looping. We have adapted components of this system to...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2005.04.035

    authors: Becker NA,Kahn JD,Maher LJ 3rd

    更新日期:2005-06-17 00:00:00

  • Crystal structure of Bacillus anthracis ThiI, a tRNA-modifying enzyme containing the predicted RNA-binding THUMP domain.

    abstract::ThiI is an enzyme responsible for the formation of the modified base S(4)U (4-thiouridine) found at position 8 in some prokaryotic tRNAs. This base acts as a sensitive trigger for the response mechanism to UV exposure, providing protection against its damaging effects. We present the crystal structure of Bacillus anth...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2005.11.013

    authors: Waterman DG,Ortiz-Lombardía M,Fogg MJ,Koonin EV,Antson AA

    更新日期:2006-02-10 00:00:00

  • Structural analysis of yeast HSF by site-specific crosslinking.

    abstract::We have introduced cysteine substitutions into the yeast HSF1 gene at a variety of locations. Most have no phenotypic effect, and therefore provide site-specific probes for thiol-specific reagents. Crosslinking of single mutants identifies locations where equivalent regions of individual monomers can approach each oth...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.4096

    authors: Bonner JJ,Chen D,Storey K,Tushan M,Lea K

    更新日期:2000-09-22 00:00:00

  • Effects of the nucleoid protein HU on the structure, flexibility, and ring-closure properties of DNA deduced from Monte Carlo simulations.

    abstract::The histone-like HU (heat unstable) protein plays a key role in the organization and regulation of the Escherichia coli genome. The nonspecific nature of HU binding to DNA complicates analysis of the mechanism by which the protein contributes to the looping of DNA. Conventional models of the looping of HU-bound duplex...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2008.05.088

    authors: Czapla L,Swigon D,Olson WK

    更新日期:2008-10-03 00:00:00

  • Stability of coliphage lambda DNA replication initiator, the lambda O protein.

    abstract::The initiator of coliphage lambda DNA replication, lambda O protein, may be detected among other 35S-labeled phage and bacterial proteins by a method based on immunoprecipitation. This method makes it possible to study lambda O proteolytic degradation in lambda plasmid-harboring or lambda phage-infected cells; it avoi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(92)90624-s

    authors: Wegrzyn G,Pawlowicz A,Taylor K

    更新日期:1992-08-05 00:00:00

  • Genetic interactions among the transmembrane segments of the G protein coupled receptor encoded by the yeast STE2 gene.

    abstract::G protein coupled receptors (GPCRs) are integral membrane proteins that mediate cellular responses to a wide variety of extracellular signals. However, the structural basis for activation of this class of receptors by ligand binding is not well understood. We report here the use of a systematic genetic protocol for id...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1996.0816

    authors: Sommers CM,Dumont ME

    更新日期:1997-02-28 00:00:00

  • Solution structure of a DNA three-way junction containing two unpaired thymidine bases. Identification of sequence features that decide conformer selection.

    abstract::The solution structure of a DNA three-way junction (3H) containing two unpaired thymidine bases at the branch site (3HT2), was determined by NMR. Arms A and B of the 3HT2 form a quasi-continuous stacked helix, which is underwound at the junction and has an increased helical rise. The unstacked arm C forms an acute ang...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.4224

    authors: van Buuren BN,Overmars FJ,Ippel JH,Altona C,Wijmenga SS

    更新日期:2000-12-01 00:00:00

  • Influence of chromatin and single strand binding proteins on the activity of an archaeal MCM.

    abstract::The mini-chromosome maintenance (MCM) complex is the presumptive replicative helicase in archaea and eukaryotes. In archaea, the MCM is a homo-multimer, in eukaryotes a heterohexamer composed of six related subunits, MCM 2-7. Biochemical studies using naked DNA templates have revealed that archaeal MCMs and a sub-comp...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.01.074

    authors: Marsh VL,McGeoch AT,Bell SD

    更新日期:2006-04-14 00:00:00

  • NMR structure of the integral membrane protein OmpX.

    abstract::The structure of the integral membrane protein OmpX from Escherichia coli reconstituted in 60 kDa DHPC micelles (OmpX/DHPC) was calculated from 526 NOE upper limit distance constraints. The structure determination was based on complete sequence-specific assignments for the amide protons and the Val, Leu, and Ile(delta...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2003.09.014

    authors: Fernández C,Hilty C,Wider G,Güntert P,Wüthrich K

    更新日期:2004-03-05 00:00:00

  • Taxonomy and conformational analysis of loops in proteins.

    abstract::We propose a general classification scheme for loops, aperiodic segments of protein structure. In an effort to avoid the geometric complexity created by non-repeating phi psi angles, a morphologic definition that focuses upon the linearity and planarity of loops is utilized. Out of 432 loops (4 to 20 residues in lengt...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(92)90553-v

    authors: Ring CS,Kneller DG,Langridge R,Cohen FE

    更新日期:1992-04-05 00:00:00

  • A continuum model for protein-protein interactions: application to the docking problem.

    abstract::The prediction of protein-protein interactions in solution is a major goal of theoretical structural biology. Here, we implement a continuum description of the thermodynamic processes involved. The model differs considerably from previous models in its use of "molecular surface" area to describe the hydrophobic compon...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1995.0375

    authors: Jackson RM,Sternberg MJ

    更新日期:1995-07-07 00:00:00

  • Mapping transition states of protein unfolding by protein engineering of ligand-binding sites.

    abstract::We describe a method for probing the integrity and relative orientation of structural elements that are indirectly linked by ligands in protein complexes during protein folding. The effect of 3'-GMP on the rate constants of unfolding of wild-type barnase and several mutants has been studied. By comparing the rates of ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(91)80188-z

    authors: Sancho J,Meiering EM,Fersht AR

    更新日期:1991-10-05 00:00:00

  • Inter-domain motions of the N-domain of the KdpFABC complex, a P-type ATPase, are not driven by ATP-induced conformational changes.

    abstract::P-type ATPases are involved in the active transport of ions across biological membranes. The KdpFABC complex (P-type ATPase) of Escherichia coli is a high-affinity K+ uptake system that operates only when the cell experiences osmotic stress or K+ limitation. Here, we present the solution structure of the nucleotide bi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2004.07.060

    authors: Haupt M,Bramkamp M,Coles M,Altendorf K,Kessler H

    更新日期:2004-10-01 00:00:00

  • Crystal structures of the S. cerevisiae Spt6 core and C-terminal tandem SH2 domain.

    abstract::The conserved and essential eukaryotic protein Spt6 functions in transcription elongation, chromatin maintenance, and RNA processing. Spt6 has three characterized functions. It is a histone chaperone capable of reassembling nucleosomes, a central component of transcription elongation complexes, and is required for rec...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2011.03.002

    authors: Close D,Johnson SJ,Sdano MA,McDonald SM,Robinson H,Formosa T,Hill CP

    更新日期:2011-05-13 00:00:00

  • The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery.

    abstract::The Myosin A-tail interacting protein (MTIP) of the malaria parasite links the actomyosin motor of the host cell invasion machinery to its inner membrane complex. We report here that at neutral pH Plasmodium falciparum MTIP in complex with Myosin A adopts a compact conformation, with its two domains completely surroun...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2007.06.016

    authors: Bosch J,Turley S,Roach CM,Daly TM,Bergman LW,Hol WG

    更新日期:2007-09-07 00:00:00

  • An improved system for the generation and analysis of mutant proteins containing unnatural amino acids in Saccharomyces cerevisiae.

    abstract::We have previously described methodology that makes it possible to genetically encode a wide array of unnatural amino acids in both prokaryotic and eukaryotic organisms. Here, we report the systematic optimization of a Saccharomyces cerevisiae expression system for the production of mutant proteins containing unnatura...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2007.05.017

    authors: Chen S,Schultz PG,Brock A

    更新日期:2007-08-03 00:00:00

  • Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia.

    abstract::TWINKLE is the helicase at the mitochondrial DNA (mtDNA) replication fork in mammalian cells. Mutations in the PEO1 gene, which encodes TWINKLE, cause autosomal dominant progressive external ophthalmoplegia (AdPEO), a disorder associated with deletions in mtDNA. Here, we characterized seven different AdPEO-causing mut...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2008.01.035

    authors: Korhonen JA,Pande V,Holmlund T,Farge G,Pham XH,Nilsson L,Falkenberg M

    更新日期:2008-03-28 00:00:00

  • Mechanism of photosensory adaptation in Halobacterium salinarium.

    abstract::Phototaxis in Halobacterium salinarium is the result of an interplay of sensory rhodopsin excitation and adaptation to the stimulus background. Adaptation to orange light, received by sensory rhodopsin I was probed by measuring the behavioral response of cells to a step-like decrease in intensity. Cells were able to a...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1994.0101

    authors: Marwan W,Bibikov SI,Montrone M,Oesterhelt D

    更新日期:1995-03-03 00:00:00

  • Crystallization and preliminary diffraction studies of hydroxypyruvate reductase (D-glycerate dehydrogenase) from Hyphomicrobium methylovorum.

    abstract::Two crystal forms of hydroxypyruvate reductase (D-glycerate dehydrogenase) from the methylotrophic bacterium Hyphomicrobium methylovorum have been grown from ammonium sulphate solutions. One crystal form is triclinic, with unit cell parameters a = 60.4 A, b = 60.5 A, c = 66.3 A, alpha = 102.3 degrees, beta = 113.7 deg...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(92)90410-l

    authors: Goldberg JD,Brick P,Yoshida T,Mitsunaga T,Oshiro T,Shimao M,Izumi Y

    更新日期:1992-06-05 00:00:00

  • Manganese superoxide dismutase from Thermus thermophilus. A structural model refined at 1.8 A resolution.

    abstract::The structure of Mn(III) superoxide dismutase (Mn(III)SOD) from Thermus thermophilus, a tetramer of chains 203 residues in length, has been refined by restrained least-squares methods. The R-factor [formula: see text] for the 54,056 unique reflections measured between 10.0 and 1.8 A (96% of all possible reflections) i...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(91)90569-r

    authors: Ludwig ML,Metzger AL,Pattridge KA,Stallings WC

    更新日期:1991-05-20 00:00:00

  • Rapid folding and unfolding of Apaf-1 CARD.

    abstract::Caspase recruitment domains (CARDs) are members of the death domain superfamily and contain six antiparallel helices in an alpha-helical Greek key topology. We have examined the equilibrium and kinetic folding of the CARD of Apaf-1 (apoptotic protease activating factor 1), which consists of 97 amino acid residues, at ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2007.02.105

    authors: Milam SL,Nicely NI,Feeney B,Mattos C,Clark AC

    更新日期:2007-05-25 00:00:00

  • Cellular remodelling of individual collagen fibrils visualized by time-lapse AFM.

    abstract::The extracellular matrix in tissues such as bone, tendon and cornea contains ordered, parallel arrays of collagen type I fibrils. Cells embedded in these matrices frequently co-align with the collagen fibrils, suggesting that ordered fibrils provide structural or signalling cues for cell polarization. To study mechani...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2007.06.078

    authors: Friedrichs J,Taubenberger A,Franz CM,Muller DJ

    更新日期:2007-09-21 00:00:00

  • A mutation in the S-switch region of the Runt domain alters the dynamics of an allosteric network responsible for CBFbeta regulation.

    abstract::The Runt domain is the DNA binding domain of the core binding factor (CBF) Runx subunits. The CBFs are transcription factors that play critical roles in hematopoiesis, bone, and neuron development in mammals. A common non-DNA binding CBFbeta subunit heterodimerizes with the Runt domain of the Runx proteins and alloste...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.10.002

    authors: Li Z,Lukasik SM,Liu Y,Grembecka J,Bielnicka I,Bushweller JH,Speck NA

    更新日期:2006-12-15 00:00:00