当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > Unveiling hidden catalytic contributions of the conserved His/Trp-III in tyrosine recombinases: assembly of a novel active site in Flp recombinase harboring alanine at this position.

Unveiling hidden catalytic contributions of the conserved His/Trp-III in tyrosine recombinases: assembly of a novel active site in Flp recombinase harboring alanine at this position.

Abstract：

:The catalytic pentad of tyrosine recombinases, that assists the tyrosine nucleophile, includes a conserved histidine/tryptophan (His/Trp-III). Flp and Cre harbor tryptophan at this position; most of their kin recombinases display histidine. Contrary to the conservation rule, Flp(W330F) is a much stronger recombinase than Flp(W330H). The hydrophobicity of Trp330 or Phe330 is utilized in correctly positioning Tyr343 during the strand cleavage step of recombination. Why then is phenylalanine almost never encountered in the recombinase family at this conserved position? Using exogenous nucleophiles and synthetic methylphosphonate or 5'-thiolate substrates, we decipher that Trp330 also assists in the activation of the scissile phosphate and the departure of the 5'-hydroxyl leaving group. These two functions are consistent with the hydrogen bonding property of Trp330 as well as its location in structures of the Flp recombination complexes. However, van der Waals contact between Trp330 and Arg308 may also be important for the phosphate activation step. A structure based suppression strategy permits the inactive variant Flp(W330A) to be rescued by a second site mutation A339M. Modeling alanine and methionine at positions 330 and 339, respectively, in the Flp crystal structure suggests a plausible mechanism for active site restoration. Successful suppression suggests the possibility of evolving, by design, new active site configurations for tyrosine recombination.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Ma CH,Kwiatek A,Bolusani S,Voziyanov Y,Jayaram M

doi

10.1016/j.jmb.2007.02.022

subject

Has Abstract

pub_date

2007-04-20 00:00:00

pages

183-96

issue

1

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(07)00203-3

journal_volume

368

pub_type

杂志文章

相关文献

JOURNAL OF MOLECULAR BIOLOGY文献大全
  • Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK.

    abstract：:Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively in skeletal muscle, where it is required for formation of the neuromuscular junction. MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. Here, we report the crystal structure of the agrin-responsive first and seco...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2006.09.019

    authors： Stiegler AL,Burden SJ,Hubbard SR

    更新日期：2006-12-01 00:00:00

  • Solution dynamics of the trp repressor: a study of amide proton exchange by T1 relaxation.

    abstract：:The amide proton exchange rates of Escherichia coli trp repressor have been measured through their effects on the longitudinal relaxation rates of the amide protons. Three types of exchange regimes have been observed: (1) slow exchange (on a minute/hour time-scale), measurable by isotope exchange, but not by relaxatio...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(05)80111-1

    authors： Gryk MR,Finucane MD,Zheng Z,Jardetzky O

    更新日期：1995-03-10 00:00:00

  • Impact of mutations on the allosteric conformational equilibrium.

    abstract：:Allostery in a protein involves effector binding at an allosteric site that changes the structure and/or dynamics at a distant, functional site. In addition to the chemical equilibrium of ligand binding, allostery involves a conformational equilibrium between one protein substate that binds the effector and a second s...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2012.11.041

    authors： Weinkam P,Chen YC,Pons J,Sali A

    更新日期：2013-02-08 00:00:00

  • Active-site determination of a pyrimidine dimer glycosylase.

    abstract：:One mechanism for the repair of UV-induced DNA damage is the base excision repair pathway. The initial step in this pathway and the specificity for the type of damage that is to be repaired reside in DNA glycosylase/abasic (AP) lyases. Cleavage of the glycosyl bond of the 5' pyrimidine of a cyclobutane pyrimidine dime...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1999.3369

    authors： Garvish JF,Lloyd RS

    更新日期：2000-01-21 00:00:00

  • Monitoring Ligand-Induced Protein Ordering in Drug Discovery.

    abstract：:While the gene for p53 is mutated in many human cancers causing loss of function, many others maintain a wild-type gene but exhibit reduced p53 tumor suppressor activity through overexpression of the negative regulators, Mdm2 and/or MdmX. For the latter mechanism of loss of function, the activity of endogenous p53 can...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2016.01.016

    authors： Grace CR,Ban D,Min J,Mayasundari A,Min L,Finch KE,Griffiths L,Bharatham N,Bashford D,Kiplin Guy R,Dyer MA,Kriwacki RW

    更新日期：2016-03-27 00:00:00

  • Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling.

    abstract：:Muscular dystrophy with myositis (mdm) is a recessive mouse mutation that is caused by a small deletion in the giant elastic muscle protein titin. Homozygous mdm/mdm mice develop a progressive muscular dystrophy, leading to death at approximately 2 months of age. We surveyed the transcriptomes of skeletal muscles from...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2003.12.021

    authors： Witt CC,Ono Y,Puschmann E,McNabb M,Wu Y,Gotthardt M,Witt SH,Haak M,Labeit D,Gregorio CC,Sorimachi H,Granzier H,Labeit S

    更新日期：2004-02-06 00:00:00

  • Functional analysis of the glutathione S-transferase 3 from Onchocerca volvulus (Ov-GST-3): a parasite GST confers increased resistance to oxidative stress in Caenorhabditis elegans.

    abstract：:This study examined the genomic organisation of the coding region of the glutathione S-transferase 3 (Ov-GST-3) from the human parasitic nematode Onchocerca volvulus; alternative splicing leads to three different transcripts (Ov-GST-3/1; Ov-GST-3/2 and Ov-GST-3/3). Since the expression of Ov-GST-3 is inducible by oxid...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(02)01174-9

    authors： Kampkötter A,Volkmann TE,de Castro SH,Leiers B,Klotz LO,Johnson TE,Link CD,Henkle-Dührsen K

    更新日期：2003-01-03 00:00:00

  • Structures of DegQ from Legionella pneumophila Define Distinct ON and OFF States.

    abstract：:HtrA (high-temperature requirement A) family proteins play important roles in protein-quality control processes in the bacterial periplasm. A common feature of all members of this family is their modular organization comprising a chymotrypsin-like protease domain and at least one PDZ (postsynaptic density of 95 kDa, d...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2015.06.023

    authors： Schubert A,Wrase R,Hilgenfeld R,Hansen G

    更新日期：2015-08-28 00:00:00

  • Conformational properties of the aggregation precursor state of HypF-N.

    abstract：:The conversion of specific proteins or protein fragments into insoluble, ordered fibrillar aggregates is a fundamental process in protein chemistry, biology, medicine and biotechnology. As this structural conversion seems to be a property shared by many proteins, understanding the mechanism of this process will be of ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.04.002

    authors： Campioni S,Mossuto MF,Torrassa S,Calloni G,de Laureto PP,Relini A,Fontana A,Chiti F

    更新日期：2008-06-06 00:00:00

  • Structure analysis of archaeal AMP phosphorylase reveals two unique modes of dimerization.

    abstract：:AMP phosphorylase (AMPpase) catalyzes the initial reaction in a novel AMP metabolic pathway recently found in archaea, converting AMP and phosphate into adenine and ribose 1,5-bisphosphate. Gel-filtration chromatography revealed that AMPpase from Thermococcus kodakarensis (Tk-AMPpase) forms an exceptionally large macr...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2013.04.026

    authors： Nishitani Y,Aono R,Nakamura A,Sato T,Atomi H,Imanaka T,Miki K

    更新日期：2013-08-09 00:00:00

  • The FGFR D3 domain determines receptor selectivity for fibroblast growth factor 21.

    abstract：:FGF21 is a member of a unique subfamily of fibroblast growth factors that function as endocrine hormones and regulate a variety of metabolic activities. Unlike paracrine FGFs, FGF21 does not bind heparin and requires βKlotho as a co-receptor to activate FGFR signaling. In the presence of βKlotho, FGF21 is able to acti...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2011.03.003

    authors： Gupte J,Yang L,Wu X,Weiszmann J,Hecht R,Lemon B,Lindberg R,Wang Z,Li Y

    更新日期：2011-05-06 00:00:00

  • Highly cooperative recruitment of Ets-1 and release of autoinhibition by Pax5.

    abstract：:Pax5 (paired box binding factor 5) is a critical regulator of transcription and lineage commitment in B lymphocytes. In B cells, mb-1 (Ig-alpha/immunoglobulin-associated alpha) promoter transcription is activated by Pax5 through its recruitment of E74-like transforming sequence (Ets) family proteins to a composite sit...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2009.07.028

    authors： Fitzsimmons D,Lukin K,Lutz R,Garvie CW,Wolberger C,Hagman J

    更新日期：2009-09-18 00:00:00

  • Structure and substrate recognition of the Escherichia coli DNA adenine methyltransferase.

    abstract：:The structure of the Escherichia coli Dam DNA-(adenine-N6)-methyltransferase in complex with cognate DNA was determined at 1.89 A resolution in the presence of S-adenosyl-L-homocysteine. DNA recognition and the dynamics of base-flipping were studied by site-directed mutagenesis, DNA methylation kinetics and fluorescen...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2006.02.028

    authors： Horton JR,Liebert K,Bekes M,Jeltsch A,Cheng X

    更新日期：2006-04-28 00:00:00

  • A GAF domain in the hypoxia/NO-inducible Mycobacterium tuberculosis DosS protein binds haem.

    abstract：:The majority of the Mycobacterium tuberculosis response to hypoxia and nitric oxide is through the DosRS (DevRS) two-component regulatory system. The N-terminal input domain of the DosS sensor contains two GAF domains. We demonstrate here that the proximal GAF domain binds haem, and identified histidine 149 of DosS as...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2005.09.011

    authors： Sardiwal S,Kendall SL,Movahedzadeh F,Rison SC,Stoker NG,Djordjevic S

    更新日期：2005-11-11 00:00:00

  • Functional significance of arginine 15 in the active site of human class alpha glutathione transferase A1-1.

    abstract：:Arg15 is a conserved active-site residue in class Alpha glutathione transferases. X-ray diffraction studies of human glutathione transferase A1-1 have shown that N epsilon of this amino acid residue is adjacent to the sulfur atom of a glutathione derivative bound to the active site, suggesting the presence of a hydrog...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(05)80154-8

    authors： Björnestedt R,Stenberg G,Widersten M,Board PG,Sinning I,Jones TA,Mannervik B

    更新日期：1995-04-07 00:00:00

  • Structure-based identification of a ricin inhibitor.

    abstract：:Ricin is a potent cytotoxin which has been used widely in the construction of therapeutic agents such as immunotoxins. Recently it has been used by governments and underground groups as a poison. There is interest in identifying and designing effective inhibitors of the ricin A chain (RTA). In this study computer-assi...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0865

    authors： Yan X,Hollis T,Svinth M,Day P,Monzingo AF,Milne GW,Robertus JD

    更新日期：1997-03-14 00:00:00

  • Crystallization and preliminary X-ray analysis of phenylalanine hydroxylase from rat liver.

    abstract：:Phenylalanine hydroxylase from rat liver has been crystallized from polyethylene glycol 4500 with sodium formate. The crystals are tetragonal rods and belong to space group P4(1)22 or P4(3)22 with unit cell dimensions a = b = 57.6 A and c = 304.1 A. They diffract to at least 2.4 A resolution and have one molecule per ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(91)90694-2

    authors： Celikel R,Davis MD,Dai XP,Kaufman S,Xuong NH

    更新日期：1991-04-05 00:00:00

  • The loop sequence plays crucial roles for isomerization of intramolecular DNA triplexes in supercoiled plasmids.

    abstract：:The effect of base composition in the central region of polypurine.polypyrimidine (Pur.Pyr) tracts on the formation of intramolecular DNA triplexes in plasmids was examined using chemical probes (diethyl pyrocarbonate and OsO4), and two-dimensional (2-D) agarose gel electrophoresis. Two isomers exist for an intramolec...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(05)80025-7

    authors： Shimizu M,Kubo K,Matsumoto U,Shindo H

    更新日期：1994-01-07 00:00:00

  • Functionally important correlated motions in the single-stranded DNA-binding protein encoded by filamentous phage Pf3.

    abstract：:To elucidate the interplay between different parts of dimeric single-stranded DNA-binding proteins we have studied the correlated motions in the protein encoded by filamentous phage Pf3 via the combined use of 15N-NMR relaxation experiments, molecular dynamics simulations and essential dynamics calculations. These stu...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1999.2629

    authors： Horstink LM,Abseher R,Nilges M,Hilbers CW

    更新日期：1999-04-02 00:00:00

  • Characterization and HIV-1 fusion inhibitory properties of monoclonal Fabs obtained from a human non-immune phage library selected against diverse epitopes of the ectodomain of HIV-1 gp41.

    abstract：:Using a human non-immune phage library comprising more than 10(9) functional human antibody specificities in Fab format, we have been able to select a set of eight monoclonal Fabs targeted against diverse epitopes of the ectodomain of gp41 from HIV-1. The antigens used for panning the antibodies comprised two soluble,...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2005.09.044

    authors： Louis JM,Bewley CA,Gustchina E,Aniana A,Clore GM

    更新日期：2005-11-11 00:00:00

  • The three-dimensional solution structure of NaD1, a new floral defensin from Nicotiana alata and its application to a homology model of the crop defense protein alfAFP.

    abstract：:NMR spectroscopy and simulated annealing calculations have been used to determine the three-dimensional structure of NaD1, a novel antifungal and insecticidal protein isolated from the flowers of Nicotiana alata. NaD1 is a basic, cysteine-rich protein of 47 residues and is the first example of a plant defensin from fl...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(02)01103-8

    authors： Lay FT,Schirra HJ,Scanlon MJ,Anderson MA,Craik DJ

    更新日期：2003-01-03 00:00:00

  • Sequence-dependent nucleosome structural and dynamic polymorphism. Potential involvement of histone H2B N-terminal tail proximal domain.

    abstract：:Relaxation of nucleosomes on an homologous series (pBR) of ca 350-370 bp DNA minicircles originating from plasmid pBR322 was recently used as a tool to study their structure and dynamics. These nucleosomes thermally fluctuated between three distinct DNA conformations within a histone N-terminal tail-modulated equilibr...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(02)01372-4

    authors： Sivolob A,Lavelle C,Prunell A

    更新日期：2003-02-07 00:00:00

  • Dynein arm substructure and the orientation of arm-microtubule attachments.

    abstract：:In the presence of AMP-PCP (beta, gamma-methyleneadenosine 5'-triphosphate), a non-hydrolyzable analog of ATP, negative stain images of increased morphological detail indicate that the dynein arm, attached to ciliary doublet microtubules, is composed of subunits including a cape, an elongated body and a head. The arra...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(84)90127-x

    authors： Avolio J,Lebduska S,Satir P

    更新日期：1984-03-05 00:00:00

  • Properties of supercoiled DNA in gel electrophoresis. The V-like dependence of mobility on topological constraint. DNA-matrix interactions.

    abstract：:The dependence of the electrophoretic mobility of small DNA rings on topological constraint was investigated in acrylamide or agarose gels as a function of DNA size (from approximately 350 to 1400 base-pairs), gel concentration and nucleotide sequence. Under appropriate adjustment between the size of the DNA and the g...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(86)90282-2

    authors： Zivanovic Y,Goulet I,Prunell A

    更新日期：1986-12-05 00:00:00

  • Determination of the cleavage site of the phage T4 prohead protease in gene product 68. Influence of protein secondary structure on cleavage specificity.

    abstract：:The cleavage site of the T4 prohead protease in gene product 68 of bacteriophage T4 has been determined by direct protein sequencing. It is located close to the carboxy-terminal end of a predicted alpha-helix in the sequence Asn-Val-Glu-Ala between the Glu and Ala residues. Secondary structure seems to be more importa...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(85)90138-x

    authors： Keller B,Kellenberger E,Bickle TA,Tsugita A

    更新日期：1985-12-05 00:00:00

  • Translational control and differential RNA decay are key elements regulating postsegregational expression of the killer protein encoded by the parB locus of plasmid R1.

    abstract：:The parB locus of plasmid R1, which mediates plasmid stability via postsegregational killing of plasmid-free cells, encodes two genes, hok and sok. The hok gene product is a potent cell-killing protein. The hok gene is regulated at the translational level by the sok gene-encoded repressor, a small anti-sense RNA compl...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(88)90096-4

    authors： Gerdes K,Helin K,Christensen OW,Løbner-Olesen A

    更新日期：1988-09-05 00:00:00

  • Engineered oligomerization state of OmpF protein through computational design decouples oligomer dissociation from unfolding.

    abstract：:Biogenesis of β-barrel membrane proteins is a complex, multistep, and as yet incompletely characterized process. The bacterial porin family is perhaps the best-studied protein family among β-barrel membrane proteins that allows diffusion of small solutes across the bacterial outer membrane. In this study, we have iden...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2012.02.043

    authors： Naveed H,Jimenez-Morales D,Tian J,Pasupuleti V,Kenney LJ,Liang J

    更新日期：2012-05-25 00:00:00

  • Structural evidence for effectiveness of darunavir and two related antiviral inhibitors against HIV-2 protease.

    abstract：:No drug has been targeted specifically for HIV-2 (human immunodeficiency virus type 2) infection despite its increasing prevalence worldwide. The antiviral HIV-1 (human immunodeficiency virus type 1) protease (PR) inhibitor darunavir and the chemically related GRL98065 and GRL06579A were designed with the same chemica...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.09.031

    authors： Kovalevsky AY,Louis JM,Aniana A,Ghosh AK,Weber IT

    更新日期：2008-12-05 00:00:00

  • Determining the Limitations and Benefits of Noise in Gene Regulation and Signal Transduction through Single Cell, Microscopy-Based Analysis.

    abstract：:Stochastic fluctuations, termed "noise," in the level of biological molecules can greatly impact cellular functions. While biological noise can sometimes be detrimental, recent studies have provided an increasing number of examples in which biological noise can be functionally beneficial. Rather than provide an exhaus...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章,评审

    doi：10.1016/j.jmb.2017.03.007

    authors： Harton MD,Batchelor E

    更新日期：2017-04-21 00:00:00

  • Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain.

    abstract：:We have identified a novel family of proteins, in which the N-terminal cystathionine beta-synthase (CBS) domain is fused to the C-terminal Zn ribbon domain. Four proteins were overexpressed in Escherichia coli and purified: TA0289 from Thermoplasma acidophilum, TV1335 from Thermoplasma volcanium, PF1953 from Pyrococcu...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2007.10.060

    authors： Proudfoot M,Sanders SA,Singer A,Zhang R,Brown G,Binkowski A,Xu L,Lukin JA,Murzin AG,Joachimiak A,Arrowsmith CH,Edwards AM,Savchenko AV,Yakunin AF

    更新日期：2008-01-04 00:00:00