Dr Jim Spencer

B.A.(Cantab.), Ph.D.(Bristol)

  • BS8 1TD

19952020

Research output per year

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Research Output

  • 70 Article (Academic Journal)
  • 1 Conference Contribution (Conference Proceeding)
  • 1 Editorial (Academic Journal)
  • 1 Review article (Academic Journal)
1995

An integrated kinetic analysis of intermediates and transition stated is protein folding reactions

Parker, MJ., Spencer, J. & Clarke, AR., 1995, In : Journal of Molecular Biology. 253, p. 771 - 786

Research output: Contribution to journalArticle (Academic Journal)

Characterisation of the structural and energetic properties of the intermediates on the folding pathways of PGK from Bacillus stearothermophilus

Parker, MJ., Burston, SG., Jackson, GS., Spencer, J., Staniforth, RA. & Clarke, AR., 1995, In : Protein Engineering. 8, p. 22 - 22 1 p.

Research output: Contribution to journalArticle (Academic Journal)

1997

Structure of a kinetic protein folding intermediate revealed by equilibrium amide exchange

Hosszu, LLP., Craven, CJ., Parker, MJ., Lorch, M., Spencer, J., Clarke, AR. & Waltho, JP., 1997, In : Nature Structural Biology. 4, p. 801 - 804

Research output: Contribution to journalArticle (Academic Journal)

2001

Alternative rate-determining steps in hydrolysis of β-lactams by Stenotrophomonas maltophilia L1 metallo-β-lactamases

Spencer, J., Clarke, AR. & Walsh, TR., 2001, 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. p. 107 - 107 1 p.

Research output: Chapter in Book/Report/Conference proceedingConference Contribution (Conference Proceeding)

Novel mechanism of hydrolysis of therapeutic β-lactams by Stenotrophomonas maltophilia L1 metallo-β-lactamase

Spencer, J., Clarke, AR. & Walsh, TR., Sep 2001, In : Journal of Biological Chemistry. 276 (36), p. 33638 - 33644 7 p.

Research output: Contribution to journalArticle (Academic Journal)

85 Citations (Scopus)

Pre-steady-state kinetic studies of mono- and binuclear metallo-beta-lactamases

Spencer, J., Simm, AM., Higgins, CS., Clarke, AR. & Walsh, TR., Aug 2001, In : Journal of Inorganic Biochemistry. 86, p. 440 - 440 1 p.

Research output: Contribution to journalArticle (Academic Journal)

2004

Over-Expression, Purification and Characterization of Metallo-beta-Lactamase ImiS from Aeromonas veronii bv. sobria

Crawford, PA., Sharma, N., Chandrasekar, S., Sigdel, T., Walsh, TR., Spencer, J. & Crowder, MW., Aug 2004, In : Protein Expression and Purification. 36, p. 272 - 279 8 p.

Research output: Contribution to journalArticle (Academic Journal)

36 Citations (Scopus)
2005

Antibiotic recognition by binuclear metallo-β-lactamases revealed by X-ray crystallography

Spencer, J., Read, J., Sessions, RB., Howell, S., Blackburn, GM. & Gamblin, SJ., Oct 2005, In : Journal of the American Chemical Society. 127 (41), p. 14439 - 14444 6 p.

Research output: Contribution to journalArticle (Academic Journal)

100 Citations (Scopus)
2006

A New Approach to the Inhibition of Metallo-beta-Lactamases

Spencer, J. & Walsh, TR., Feb 2006, In : Angewandte Chemie - International Edition. 45, p. 1022 - 1026 5 p.

Research output: Contribution to journalArticle (Academic Journal)

40 Citations (Scopus)

Crystal Structure of Pseudomonas aeruginosa SPM-1 Provides Insights into Variable Zinc Affinity of Metallo-β-lactamases

Murphy, TA., Catto, LE., Halford, SE., Hadfield, AT., Minor, W., Walsh, TR. & Spencer, J., Mar 2006, In : Journal of Molecular Biology. 357 (3), p. 890 - 903 14 p.

Research output: Contribution to journalArticle (Academic Journal)

70 Citations (Scopus)

Metallo-beta-lactamases: novel weaponry for antibiotic resistance in bacteria

Crowder, MW., Spencer, J. & Vila, AJ., Oct 2006, In : Accounts of Chemical Research. 39, p. 721 - 728

Research output: Contribution to journalArticle (Academic Journal)

274 Citations (Scopus)

Metallo-β-lactamasen: ein neuer Inhibitionsansatz

Spencer, J. & Walsh, TR., Feb 2006, In : Angewandte Chemie. 118, 7, p. 1038-1042 5 p.

Research output: Contribution to journalArticle (Academic Journal)

2007

Structural basis for the role of Asp-120 in metallo-beta-lactamases

Crisp, JC., Conners, R., Garrity, JD., Carenbauer, AL., Crowder, MW. & Spencer, J., Sep 2007, In : Biochemistry. 46 (37), p. 10664 - 10674 11 p.

Research output: Contribution to journalArticle (Academic Journal)

25 Citations (Scopus)
2008

Kinetic characterization of VIM-7, a divergent member of the VIM metallo-beta-lactamase family

Samuelsen, O., Castanheira, M., Walsh, TR. & Spencer, J., Aug 2008, In : Antimicrobial Agents and Chemotherapy. 52, 8, p. 2905 - 2908 4 p.

Research output: Contribution to journalArticle (Academic Journal)

25 Citations (Scopus)
2009

Approaches to the simultaneous inactivation of metallo- and serine-beta-lactamases

Ganta, SR., Perumal, S., Pagadala, SR., Samuelsen, O., Spencer, J., Pratt, RF. & Buynak, JD., Feb 2009, In : Bioorganic and Medicinal Chemistry Letters. 19, p. 1618 - 1622 5 p.

Research output: Contribution to journalArticle (Academic Journal)

22 Citations (Scopus)

RE coil: an antimicrobial peptide regulator

Ryadnov, MG., Mukamolova, GV., Hawrani, AS., Spencer, J. & Platt, R., 14 Dec 2009, In : Angewandte Chemie - International Edition. 48, 51, p. 9676 - 9679 4 p.

Research output: Contribution to journalArticle (Academic Journal)

13 Citations (Scopus)
2010

Crystal structure of the LasA virulence factor from Pseudomonas aeruginosa: substrate specificity and mechanism of M23 metallopeptidases

Spencer, J., Murphy, LM., Conners, R., Sessions, RB. & Gamblin, SJ., Mar 2010, In : Journal of Molecular Biology. 396 (4), p. 908 - 923 16 p.

Research output: Contribution to journalArticle (Academic Journal)

28 Citations (Scopus)

High-level expression and reconstitution of active Cfr, a radical-SAM rRNA methyltransferase that confers resistance to ribosome-acting antibiotics

Booth, MPS., Challand, MR., Emery, DC., Roach, PL. & Spencer, J., Dec 2010, In : Protein Expression and Purification. 74, p. 204 - 210 7 p.

Research output: Contribution to journalArticle (Academic Journal)

12 Citations (Scopus)
2011

Biochemical characterization of Sfh-I, the subclass B2 metallo-{beta}-lactamase from Serratia fonticola UTAD54

Fonseca, MF., Arthur, CJ., Bromley, EHC., Samyn, B., Moerman, P., Saavedra, MJ., Correia, A. & Spencer, J., Nov 2011, In : Antimicrobial Agents and Chemotherapy. 55, p. 5392 - 5395 4 p.

Research output: Contribution to journalArticle (Academic Journal)

9 Citations (Scopus)

Crystal structure of Serratia fonticola Sfh-I: activation of the nucleophile in mono-zinc metallo-β-lactamases

Fonseca, MF., Bromley, EHC., Saavedra, MJ., Correia, A. & Spencer, J., Jul 2011, In : Journal of Molecular Biology. 411, p. 951 - 959 9 p.

Research output: Contribution to journalArticle (Academic Journal)

32 Citations (Scopus)

Structural and computational investigations of VIM-7: insights into the substrate specificity of vim metallo-β-lactamases

Borra, PS., Leiros, HK., Ahmad, R., Spencer, J., Leiros, I., Walsh, TR., Sundsfjord, A. & Samuelsen, O., Aug 2011, In : Journal of Molecular Biology. 411, p. 174 - 189 16 p.

Research output: Contribution to journalArticle (Academic Journal)

29 Citations (Scopus)

Structural insights into quinolone antibiotic resistance mediated by pentapeptide repeat proteins: conserved surface loops direct the activity of a Qnr protein from a Gram-negative bacterium

Xiong, X., Bromley, EHC., Oelschlaeger, P., Woolfson, DN. & Spencer, J., May 2011, In : Nucleic Acids Research. 39, 9, p. 3917 - 3927 11 p.

Research output: Contribution to journalArticle (Academic Journal)

45 Citations (Scopus)
2012

The Basis for Carbapenem Hydrolysis by Class A β-Lactamases: A Combined Investigation using Crystallography and Simulations.

Fonseca, M. F., Chudyk, E. I., Van der Kamp, M. W., Correia, A., Mulholland, A. J. & Spencer, J., 7 Nov 2012, In : Journal of the American Chemical Society. 134, 44, p. 18275-18285 11 p.

Research output: Contribution to journalArticle (Academic Journal)

45 Citations (Scopus)
2014

Molecular basis of non-mutational derepression of ramA in Klebsiella pneumoniae

De Majumdar, S., Yu, J., Spencer, J., Tikhonova, I. G. & Schneiders, T., Oct 2014, In : Journal of Antimicrobial Chemotherapy. 69, 10, p. 2681-9 9 p.

Research output: Contribution to journalArticle (Academic Journal)

6 Citations (Scopus)

QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

Chudyk, E. I., Limb, M. A. L., Jones, C., Spencer, J., van der Kamp, M. W. & Mulholland, A. J., 7 Dec 2014, In : Chemical Communications. 50, 94, p. 14736-14739 4 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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21 Citations (Scopus)
258 Downloads (Pure)

Rhodanine hydrolysis leads to potent thioenolate mediated metallo-β-lactamase inhibition

Brem, J., van Berkel, S. S., Aik, W., Rydzik, A. M., Avison, M. B., Pettinati, I., Umland, K-D., Kawamura, A., Spencer, J., Claridge, T. D. W., McDonough, M. A. & Schofield, C. J., Dec 2014, In : Nature Chemistry. 6, 12, p. 1084-90 7 p.

Research output: Contribution to journalArticle (Academic Journal)

67 Citations (Scopus)
2015

Arginine-containing peptides as potent inhibitors of VIM-2 metallo-β-lactamase

Rotondo, C. M., Marrone, L., Goodfellow, V. J., Ghavami, A., Labbé, G., Spencer, J., Dmitrienko, G. I. & Siemann, S., Nov 2015, In : Biochimica et Biophysica Acta (BBA) - General Subjects. 1850, 11, p. 2228-38 11 p.

Research output: Contribution to journalArticle (Academic Journal)

5 Citations (Scopus)

Assay for drug discovery: Synthesis and testing of nitrocefin analogues for use as β-lactamase substrates

Ghavami, A., Labbé, G., Brem, J., Goodfellow, V. J., Marrone, L., Tanner, C. A., King, D. T., Lam, M., Strynadka, N. C. J., Pillai, D. R., Siemann, S., Spencer, J., Schofield, C. J. & Dmitrienko, G. I., 1 Oct 2015, In : Analytical Biochemistry. 486, p. 75-7 3 p.

Research output: Contribution to journalArticle (Academic Journal)

7 Citations (Scopus)

Bisthiazolidines: A Substrate-Mimicking Scaffold as an Inhibitor of the NDM-1 Carbapenemase

González, M. M., Kosmopoulou, M., Mojica, M. F., Castillo, V., Hinchliffe, P., Pettinati, I., Brem, J., Schofield, C. J., Mahler, G., Bonomo, R. A., Llarrull, L. I., Spencer, J. & Vila, A. J., 13 Nov 2015, In : ACS Infectious Diseases. 1, 11, p. 544-54 11 p.

Research output: Contribution to journalArticle (Academic Journal)

53 Citations (Scopus)

Crystal Structure of DIM-1, an Acquired Subclass B1 Metallo-β-Lactamase from Pseudomonas stutzeri

Booth, M. P. S., Kosmopoulou, M., Poirel, L., Nordmann, P. & Spencer, J., 2015, In : PLoS ONE. 10, 10, p. e0140059

Research output: Contribution to journalArticle (Academic Journal)

2 Citations (Scopus)

Exploring the Role of Residue 228 in Substrate and Inhibitor Recognition by VIM Metallo-β-lactamases

Mojica, M. F., Mahler, S. G., Bethel, C. R., Taracila, M. A., Kosmopoulou, M., Papp-Wallace, K. M., Llarrull, L. I., Wilson, B. M., Marshall, S. H., Wallace, C. J., Villegas, M. V., Harris, M. E., Vila, A. J., Spencer, J. & Bonomo, R. A., 26 May 2015, In : Biochemistry. 54, 20, p. 3183-96 14 p.

Research output: Contribution to journalArticle (Academic Journal)

24 Citations (Scopus)

Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1

Brem, J., Struwe, W. B., Rydzik, A. M., Tarhonskaya, H., Pfeffer, I., Flashman, E., van Berkel, S. S., Spencer, J., Claridge, T. D. W., McDonough, M. A., Benesch, J. L. P. & Schofield, C. J., 19 Feb 2015, In : Chemical Science. 6, 2, p. 956-963 8 p.

Research output: Contribution to journalArticle (Academic Journal)

26 Citations (Scopus)
2016
Open Access
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2 Citations (Scopus)
279 Downloads (Pure)

Cross-class metallo-β-lactamase inhibition by bisthiazolidines reveals multiple binding modes

Hinchliffe, P., Gonzalez, M. M., Mojica, M. F., Gonzalez, J. M., Castillo, V., Saiz, C., Kosmopoulou, M., Tooke, C., Llarrull, L., Mahler, G., Bonomo, R. A., Villa, A. J. & Spencer, J., 28 Jun 2016, In : Proceedings of the National Academy of Sciences of the United States of America. 113, 26, p. E3745-E3754 10 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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51 Citations (Scopus)
284 Downloads (Pure)

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study

Liu, Y-Y., Wang, Y., Walsh, T. R., Yi, L-X., Zhang, R., Spencer, J., Doi, Y., Tian, G., Dong, B., Huang, X., Yu, L-F., Gu, D., Ren, H., Chen, X., Lv, L., He, D., Zhou, H., Liang, Z., Liu, J-H. & Shen, J., 1 Feb 2016, In : Lancet Infectious Diseases. 16, 2, p. 161-168 8 p.

Research output: Contribution to journalArticle (Academic Journal)

1994 Citations (Scopus)

Role of Residues W228 and Y233 in the Structure and Activity of Metallo-β-Lactamase GIM-1

Skagseth, S., Carlsen, T. J., Bjerga, G. E. K., Spencer, J., Samuelsen, Ø. & Leiros, H-K. S., Feb 2016, In : Antimicrobial Agents and Chemotherapy. 60, 2, p. 990-1002 13 p.

Research output: Contribution to journalArticle (Academic Journal)

7 Citations (Scopus)

Sideromimic Modification of Lactivicin Dramatically Increases Potency against Extensively Drug-Resistant Stenotrophomonas maltophilia Clinical Isolates

Calvopiña, K., Umland, K-D., Rydzik, A. M., Hinchliffe, P., Brem, J., Spencer, J., Schofield, C. J. & Avison, M. B., Jul 2016, In : Antimicrobial Agents and Chemotherapy. 60, 7, p. 4170-4175 6 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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7 Citations (Scopus)
137 Downloads (Pure)

Structural and Biochemical Characterization of Rm3, a SubClass B3 Metallo- β-Lactamase Identified from a Functional Metagenomic Study

Salimraj, R., Zhang, L., Hinchliffe, P., Wellington, E. M. H., Brem, J., Schofield, C. J., Gaze, W. & Spencer, J., Oct 2016, In : Antimicrobial Agents and Chemotherapy. 60, 9, p. 5828-5840 13 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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9 Citations (Scopus)
338 Downloads (Pure)

Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates

Brem, J., Cain, R., Cahill, S., McDonough, M. A., Clifton, I. J., Jiménez-Castellanos, J-C., Avison, M. B., Spencer, J., Fishwick, C. W. G. & Schofield, C. J., 8 Aug 2016, In : Nature Communications. 7, 8 p., 12406.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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107 Citations (Scopus)
342 Downloads (Pure)
2017
Open Access
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16 Citations (Scopus)
270 Downloads (Pure)

13C-Carbamylation as a mechanistic probe for the inhibition of class D β-lactamases by avibactam and halide ions

Lohans, C. T., Wang, D. Y., Jorgensan, C., Cahill, S. T., Clifton, I. J., McDonough, M. A., Oswin, H., Spencer, J., Domene, C., Claridge, T. D. W., Brem, J. & Schofield, C. J., 28 Jul 2017, In : Organic and Biomolecular Chemistry. 15, 28, p. 6024-6032 9 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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8 Citations (Scopus)
345 Downloads (Pure)

19F-NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo-β-Lactamase

Abboud, M. I., Hinchliffe, P., Brem, J., Macsics, R., Pfeffer, I., Makena, A., Umland, K-D., Rydzik, A. M., Li, G-B., Spencer, J., Claridge, T. D. W. & Schofield, C. J., 22 Mar 2017, In : Angewandte Chemie - International Edition. 56, 14, p. 3862–3866 5 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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14 Citations (Scopus)
242 Downloads (Pure)

A general reaction mechanism for carbapenem hydrolysis by mononuclear and binuclear metallo-β-lactamases

Lisa, M. N., Palacios, A. R., Aitha, M., González, M. M., Moreno, DI. M., Crowder, M. W., Bonomo, R. A., Spencer, J., Tierney, D. L., Llarrull, L. I. & Vila, A. J., 14 Sep 2017, In : Nature Communications. 8, 538.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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38 Citations (Scopus)
218 Downloads (Pure)

Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms

Yang, Q., Li, M., Spiller, O. B., Andrey, D. O., Hinchliffe, P., Li, H., MacLean, C., Niumsup, P., Powell, L., Pritchard, M., Papkou, A., Shen, Y., Portal, E., Sands, K., Spencer, J., Tansawai, U., Thomas, D., Wang, S., Wang, Y., Shen, J. & 1 others, Walsh, T., Dec 2017, In : Nature Communications. 8, 12 p., 2054.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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36 Citations (Scopus)
262 Downloads (Pure)

Crystallographic analyses of isoquinoline complexes reveal a new mode of metallo-β-lactamase inhibition

Li, G-B., Brem, J., Abboud, M. I., Lohans, C. T., Clifton, I. J., Jiménez-Castellanos, J-C., Avison, M. B., Spencer, J., McDonough, M. A. & Schofield, C. J., 30 May 2017, In : Chemical Communications. 53, 43, p. 5806-5809 4 p.

Research output: Contribution to journalArticle (Academic Journal)

17 Citations (Scopus)

Cyclic Boronates Inhibit All Classes of β-Lactamases

Cahill, S. T., Cain, R., Wang, D. Y., Lohans, C. T., Wareham, D. W., Oswin, H. P., Mohammed, J., Spencer, J., Fishwick, C. W. G., McDonough, M. A., Schofield, C. J. & Brem, J., Apr 2017, In : Antimicrobial Agents and Chemotherapy. 61, 4, 13 p., e02260-16.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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52 Citations (Scopus)
559 Downloads (Pure)

Cyclobutanone Mimics of Intermediates in Metallo-β-Lactamase Catalysis

Abboud, M. I., Kosmopoulou, M., Krismanich, A. P., Johnson, J. W., Hinchliffe, P., Brem, J., Claridge, T. D. W., Spencer, J., Schofield, C. J. & Dmitrienko, G. I., 17 Dec 2017, In : Chemistry - A European Journal. 5 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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12 Citations (Scopus)
216 Downloads (Pure)

Insights into the Mechanistic Basis of Plasmid-Mediated Colistin Resistance from the Crystal Structure of the Catalytic Domain of MCR-1

Hinchliffe, P., Yang, Q., Portal, E., Young, T., Li, H., Tooke, C., Mendes de Carvalho, M., Paterson, N., Brem, J., Ritivirool, P., Tansawai, U., Lei, L., Li, M., Shen, Z., Wang, Y., Schofield, C., Mulholland, A., Shen, J., Walsh, T., Fey, N. & 1 others, Spencer, J., 6 Jan 2017, In : Scientific Reports. 7, 10 p., 39392 .

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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54 Citations (Scopus)
218 Downloads (Pure)

NMR-filtered virtual screening leads to non-metal chelating metallo-β-lactamase inhibitors

Li, G-B., Abboud, M. I., Brem, J., Someya, H., Lohans, C. T., Yang, S-Y., Spencer, J., Wareham, D. W., McDonough, M. A. & Schofield, C. J., 1 Feb 2017, In : Chemical Science. 8, 2, p. 928-937 10 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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37 Citations (Scopus)
116 Downloads (Pure)

Structural/mechanistic insights into the efficacy of nonclassical β-lactamase inhibitors against extensively drug resistant Stenotrophomonas maltophilia clinical isolates

Calvopina Tapia, K., Hinchliffe, P., Brem, J., Heesom, K. J., Johnson, S., Cain, R., Lohans, C. T., Fishwick, C. W. G., Schofield, C. J., Spencer, J. & Avison, M. B., 23 Oct 2017, In : Molecular Microbiology. 106, 3, p. 492–504 13 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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17 Citations (Scopus)
263 Downloads (Pure)