Research Topics
| Timothy D H BuggSummaryAffiliation: University of Warwick Country: UK Publications
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Detail Information
Publications
Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurFCatherine Paradis-Bleau
Département de Biologie médicale, Universite Laval, Sainte Foy, Quebec G1K 7P4, Canada
BMC Biochem 9:33. 2008..As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme...
Phospho-MurNAc-pentapeptide translocase (MraY) as a target for antibacterial agents and antibacterial proteinsTimothy D H Bugg
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Infect Disord Drug Targets 6:85-106. 2006..The availability of high throughput assays and prospects of MraY as an antibacterial target are also discussed...- Diverse catalytic activities in the alphabeta-hydrolase family of enzymes: activation of H2O, HCN, H2O2, and O2Timothy D H Bugg
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Bioorg Chem 32:367-75. 2004..One common feature of these novel activities is the activation of a small diatomic molecule, but via diverse chemistry. Possible mechanisms of catalysis are discussed... 
Non-heme iron-dependent dioxygenases: unravelling catalytic mechanisms for complex enzymatic oxidationsTimothy D H Bugg
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Curr Opin Chem Biol 12:134-40. 2008..The article reviews recent developments in the study of the reaction mechanisms of non-heme iron-dependent dioxygenase enzymes, especially the catechol dioxygenases and arene (Rieske) dioxygenases...- The emerging role for bacteria in lignin degradation and bio-product formationTimothy D H Bugg
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Curr Opin Biotechnol 22:394-400. 2011..If biocatalytic routes for lignin breakdown could be developed, then lignin represents a potentially rich source of renewable aromatic chemicals... - Bacterial cell wall assembly: still an attractive antibacterial targetTimothy D H Bugg
Department of Chemistry, University of Warwick, Coventry CV47AL, UK
Trends Biotechnol 29:167-73. 2011.... - Pathways for degradation of lignin in bacteria and fungiTimothy D H Bugg
Department of Chemistry, University of Warwick, Coventry, UK
Nat Prod Rep 28:1883-96. 2011.... - Catalytic role for arginine 188 in the C-C hydrolase catalytic mechanism for Escherichia coli MhpC and Burkholderia xenovorans LB400 BphDChen Li
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Biochemistry 45:12470-9. 2006.... - Kinetic characterization of lipid II-Ala:alanyl-tRNA ligase (MurN) from Streptococcus pneumoniae using semisynthetic aminoacyl-lipid II substratesGianfranco de Pascale
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, United Kingdom
J Biol Chem 283:34571-9. 2008..pneumoniae, with ligase MurM showing the major difference between penicillin-resistant and penicillin-sensitive strains... - Characterization of tRNA-dependent peptide bond formation by MurM in the synthesis of Streptococcus pneumoniae peptidoglycanAdrian J Lloyd
Departments of Biological Sciences and Chemistry, University of Warwick, Gibbet Hill Road, Coventry, United Kingdom
J Biol Chem 283:6402-17. 2008..It is anticipated that definition of the minimal structural features of MurM substrates will allow development of novel resistance inhibitors that will restore the efficacy of beta-lactams for treatment of pneumococcal infection... - Structure and mechanism of HpcH: a metal ion dependent class II aldolase from the homoprotocatechuate degradation pathway of Escherichia coliDean Rea
Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK
J Mol Biol 373:866-76. 2007..6 A and 2.0 A, respectively. Comparison with similar structures of the homologous 2-dehydro-3-deoxygalactarate aldolase, coupled with site-directed mutagenesis data, implicate histidine 45 and arginine 70 as key catalytic residues... - Investigation of a general base mechanism for ester hydrolysis in C-C hydrolase enzymes of the alpha/beta-hydrolase superfamily: a novel mechanism for the serine catalytic triadJian Jun Li
Department of Chemistry, University of Warwick, Coventry, UK CV4 7AL
Org Biomol Chem 5:507-13. 2007.... - Fluorescent reagents for in vitro studies of lipid-linked steps of bacterial peptidoglycan biosynthesis: derivatives of UDPMurNAc-pentapeptide containing d-cysteine at position 4 or 5James A Schouten
Department of Chemistry, University of Warwick, Coventry, UK CV4 7AL
Mol Biosyst 2:484-91. 2006..Pyrene-labelled lipid intermediates I and II can be generated using Micrococcus flavus membranes, enabling the study of the later lipid-linked steps... - Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitorsElena Cressina
Department of Chemistry, University of Warwick, Coventry, UK
Bioorg Med Chem 17:3443-55. 2009..These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria... - Evidence for a gem-diol reaction intermediate in bacterial C-C hydrolase enzymes BphD and MhpC from 13C NMR spectroscopyJian Jun Li
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Biochemistry 45:12461-9. 2006..The direct observation of a gem-diol intermediate provides further evidence that supports a general base mechanism for this family of enzymes... - Catalytic mechanism of C-C hydrolase MhpC from Escherichia coli: kinetic analysis of His263 and Ser110 site-directed mutantsChen Li
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
J Mol Biol 346:241-51. 2005..A catalytic mechanism is proposed involving stabilisation of reactive intermediates and activation of a nucleophilic water molecule by Ser110... - Directed evolution of a non-heme-iron-dependent extradiol catechol dioxygenase: identification of mutants with intradiol oxidative cleavage activityJanne Schlosrich
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
Chembiochem 7:1899-908. 2006.... - Interaction of the transmembrane domain of lysis protein E from bacteriophage phiX174 with bacterial translocase MraY and peptidyl-prolyl isomerase SlyDSharon Mendel
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Microbiology 152:2959-67. 2006..These results imply that the interaction of E with MraY is not at the MraY active site, and suggest that a protein-protein interaction is formed between E and MraY at a site within the transmembrane region... - Crystal structure and functional assignment of YfaU, a metal ion dependent class II aldolase from Escherichia coli K12Dean Rea
Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, UK
Biochemistry 47:9955-65. 2008..Crystal structures suggest these enzymes use an Asp-His intersubunit dyad to activate a metal-bound water or hydroxide for proton transfer during catalysis... - Investigation of acid-base catalysis in the extradiol and intradiol catechol dioxygenase reactions using a broad specificity mutant enzyme and model chemistryMichela Brivio
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
Org Biomol Chem 7:1368-73. 2009..It is therefore proposed that bifunctional acid-base catalysis is required for iron (ii)-dependent extradiol catechol cleavage, whereas the rate-determining step for intradiol catechol cleavage does not involve acid-base catalysis... - Catalytic promiscuity in the alpha/beta-hydrolase superfamily: hydroxamic acid formation, C--C bond formation, ester and thioester hydrolysis in the C--C hydrolase familyChen Li
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Chembiochem 9:71-6. 2008..The results provide experimental support for the catalytic promiscuity shown in this family of enzymes, and indicate that differences in catalytic function can be introduced by point mutations... - Adenosine phosphonate inhibitors of lipid II: alanyl tRNA ligase MurM from Streptococcus pneumoniaeElena Cressina
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Bioorg Med Chem Lett 17:4654-6. 2007..Adenosine and 2'-deoxyadenosine phosphonate transition state analogues act as the first inhibitors for the MurMN/FemABX family of tRNA-dependent ligases implicated in high-level penicillin resistance in gram-positive bacteria... - Identification of DypB from Rhodococcus jostii RHA1 as a lignin peroxidaseMark Ahmad
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Biochemistry 50:5096-107. 2011..jostii RHA1, is able to oxidize both polymeric lignin and a lignin model compound, and appears to have both Mn(II) and lignin oxidation sites. This is the first detailed characterization of a recombinant bacterial lignin peroxidase... - Inhibition of Escherichia coli glycosyltransferase MurG and Mycobacterium tuberculosis Gal transferase by uridine-linked transition state mimicsAmy E Trunkfield
Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom
Bioorg Med Chem 18:2651-63. 2010..The library was also tested against Mycobacterium tuberculosis galactosyltransferase GlfT2, and one compound showed effective inhibition at 1mM concentration... - Acid-base catalysis in the extradiol catechol dioxygenase reaction mechanism: site-directed mutagenesis of His-115 and His-179 in Escherichia coli 2,3-dihydroxyphenylpropionate 1,2-dioxygenase (MhpB)Sharon Mendel
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Biochemistry 43:13390-6. 2004..A catalytic mechanism involving His-179 and His-115 as acid-base catalytic residues is proposed... - Expression, purification, crystallization and preliminary characterization of uridine 5'-diphospho-N-acetylmuramoyl L-alanyl-D-glutamate:lysine ligase (MurE) from Streptococcus pneumoniae 110K/70Anne M Blewett
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, England
Acta Crystallogr D Biol Crystallogr 60:359-61. 2004..4, c = 74.8 A, alpha = 73.4, beta = 80.5, gamma = 72.3 degrees. Crystals grown in the presence of UDP-MurNAc-L-Ala-D-Glu alone belong to space group P2(1), with unit-cell parameters a = 71.1, b = 129.4, c = 74.6 A, beta = 106.3 degrees... - Evidence from mechanistic probes for distinct hydroperoxide rearrangement mechanisms in the intradiol and extradiol catechol dioxygenasesMeite Xin
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
J Am Chem Soc 130:10422-30. 2008.... - Synthetic 6-aryl-2-hydroxy-6-ketohexa-2,4-dienoic acid substrates for C-C hydrolase BphD: investigation of a general base catalytic mechanismDamian M Speare
Department of Chemistry, University of Warwick, Coventry, UK
Org Biomol Chem 2:2942-50. 2004..A series of para-substituted 2-hydroxy-6-keto-6-phenylhexa-2,4-dienoic acid substrates were assayed against BphD, and the derived Hammett plot (rho=-0.71) is consistent with a departing carbanion in the transition state for C-C cleavage... - Development of novel assays for lignin degradation: comparative analysis of bacterial and fungal lignin degradersMark Ahmad
Department of Chemistry, University of Warwick, Coventry, UK CV4 7AL
Mol Biosyst 6:815-21. 2010..These assays could be used to identify novel lignin degraders for breakdown of plant lignocellulose... - Expression, purification and preliminary crystallographic analysis of 2,4-dihydroxy-hepta-2-ene-1,7-dioate aldolase (HpcH) from Escherichia coli CDean Rea
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, England
Acta Crystallograph Sect F Struct Biol Cryst Commun 61:821-4. 2005..5 belong to space group I222, with unit-cell parameters a = 133.39, b = 155.39, c = 168.80 A. Complete data sets were collected to 1.6 and 2.0 A from type I and type II crystals, respectively, using synchrotron radiation... - Phospho-N-acetyl-muramyl-pentapeptide translocase from Escherichia coli: catalytic role of conserved aspartic acid residuesAdrian J Lloyd
Department of Chemistry, University of Warwick, Coventry, United Kingdom
J Bacteriol 186:1747-57. 2004.... - Biomimetic formation of 2-tropolones by dioxygenase-catalysed ring expansion of substituted 2,4-cyclohexadienonesMeite Xin
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
Chembiochem 11:272-6. 2010..This is a novel transformation for non-haem iron-dependent enzymes, and this is the first experimental demonstration of the proposed ring-expansion reaction in tropolone biosynthesis... - Detection of Staphylococcus aureus cell walls by enzyme-linked immunoassay using antibodies prepared from a semi-synthetic peptidoglycan precursorSandeep Sandhu
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
Analyst 137:1130-6. 2012..These data demonstrate that it is possible to generate antibodies with high affinity and selectivity for the (Gly)(5) containing monomer in S. aureus peptidoglycan, that could be used to develop an immunoassay for S. aureus... - 2-hydroxy-6-keto-nona-2,4-diene 1,9-dioic acid 5,6-hydrolase: evidence from 18O isotope exchange for gem-diol intermediateTimothy D H Bugg
Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom
Methods Enzymol 354:106-18. 2002 - Identification of a novel beta-replacement reaction in the biosynthesis of 2,3-diaminobutyric acid in peptidylnucleoside mureidomycin AWai Ho Lam
University of Warwick, Department of Chemistry, Coventry, United Kingdom
Org Biomol Chem 6:1912-7. 2008..These results are consistent with literature proposals for the biosynthesis of 2,3-diaminopropanoic acid from the viomycin biosynthetic gene cluster... - Synthesis and activity of 5'-uridinyl dipeptide analogues mimicking the amino terminal peptide chain of nucleoside antibiotic mureidomycin ANigel I Howard
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
Bioorg Med Chem 11:3083-99. 2003..Enzyme inhibition was shown to be competitive with Mg(2+). It is proposed that the primary amino terminus of the inhibitor binds in place of the Mg(2+) cofactor at the MraY active site, positioned via a cis-N-methyl amide linkage... - Multivalent conjugates of poly-gamma-D-glutamic acid from Bacillus licheniformis with antibody F(ab') and glycopeptide ligandsEmmanuel J F Prodhomme
Department of Chemistry, University of Warwick, Coventry, UK
Bioconjug Chem 14:1148-55. 2003..The PGA-vancomycin conjugate showed slightly lower antibacterial activity than free vancomycin versus susceptible Bacillus subtilis, but slightly higher activity versus intrinsically resistant Leuconostoc mesenteroides... - A density functional investigation of the extradiol cleavage mechanism in non-heme iron catechol dioxygenasesRobert J Deeth
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
J Biol Inorg Chem 8:409-18. 2003..The subsequent collapse of the epoxide, attack by the coordinated hydroxide and final product formation proceeds with an overall exoergicity of approximately 75 kcal mol(-1) on the U4 surface... - Biological properties of N-acyl and N-haloacetyl neuraminic acids: processing by enzymes of sialic acid metabolism, and interaction with influenza virusAndrew J Humphrey
Department of Chemistry, University of Southampton, Highfield, Southampton, UK
Bioorg Med Chem 10:3175-85. 2002..CMP-N-propionyl neuraminic acid was found not to be a substrate for CMP-N-acetyl neuraminic acid hydroxylase from pig submandibular gland... - The biosynthesis of peptidoglycan lipid-linked intermediatesAhmed Bouhss
Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moleculaire et Cellulaire, UMR 8619 CNRS, Univ Paris Sud, Orsay, France
FEMS Microbiol Rev 32:208-33. 2008..Enzyme inhibitors and antibacterial compounds interfering with these essential metabolic steps and interesting targets are presented... - Recent advances in antimicrobial nucleoside antibiotics targeting cell wall biosynthesisKen-ichi Kimura
Department of Agro-bioscience, Iwate University, Iwate 020-8550, Japan
Nat Prod Rep 20:252-73. 2003..In this review we will describe three nucleoside translocase I inhibitors, mureidomycin, tunicamycin and liposidomycin... - Antibiotic action and peptidoglycan formation on tethered lipid bilayer membranesMichael J Spencelayh
Centre for Self-Organising Molecular systems University of Leeds, Leeds, LS2 9JT, UK
Angew Chem Int Ed Engl 45:2111-6. 2006 - Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzymeCatherine Paradis-Bleau
CREFSIP, Département de Biologie médicale, Faculte de Medecine, Universite Laval, Sainte Foy, Quebec, Canada G1K 7P4
Peptides 27:1693-700. 2006..The approach proposed and results obtained suggest that efficient peptide inhibitors as well as protein-protein interaction domains can be identified by phage display... - Arene cis-dihydrodiol formation: from biology to applicationDerek R Boyd
School of Chemistry and Centre for Theory and Application of Catalysis, Queen's University of Belfast, Belfast, UKBT9 5AG
Org Biomol Chem 4:181-92. 2006.... - Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and evaluation as MraY inhibitorsXiu Hua Xu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 354 Fenglin Lu, Shanghai 200032, China
Org Biomol Chem 6:157-61. 2008..This unusual process may be correlated with the presence of the electron-withdrawing gem-difluoro substituents at the C-2 position of furanose. Compound 3 demonstrated 29% inhibition of MraY at 11.4 mM...