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)
Article (Academic Journal)
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)

An Efficient Computational Assay for β-Lactam Antibiotic Breakdown by Class A β-Lactamases

Hirvonen, V., Hammond, K., Chudyk, E., Limb, M., Spencer, J., Mulholland, A. & Van der Kamp, M., 30 Jul 2019, In : Journal of Chemical Information and Modeling. 59, 8, p. 3365-3369 5 p.

Research output: Contribution to journalArticle (Academic Journal)

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

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)

A New Mechanism for β-Lactamases: Class D Enzymes Degrade 1β-Methyl Carbapenems through Lactone Formation

Lohans, C. T., van Groesen, E., Kumar, K., Tooke, C. L., Spencer, J., Paton, R. S., Brem, J. & Schofield, C. J., Jan 2018, In : Angewandte Chemie - International Edition. 57, 5, p. 1282-1285 4 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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6 Citations (Scopus)
163 Downloads (Pure)

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)

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)

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)

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)

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)

Bicyclic Boronate VNRX-5133 Inhibits Metallo- and Serine-β-Lactamases

Krajnc, A., Brem, J., Hinchliffe, P., Calvopina, K. A., Panduwawala, T. D., Lang, P., Kamps, J. J. A. G., Tyrrell, J. M., Widlake, E., Saward, B. G., Walsh, T. R., Spencer, J. & Schofield, C. J., 27 Aug 2019, In : Journal of Medicinal Chemistry. 62, 18, p. 8544-8556 13 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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28 Citations (Scopus)
176 Downloads (Pure)

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)

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

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)

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)

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)

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)

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)

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)

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)

Crystal structures of VIM-1 complexes explain active site heterogeneity in VIM-class metallo-β-lactamases

Salimraj, R., Hinchliffe, P., Kosmopoulou, M., Tyrrell, J. M., Brem, J., van Berkel, S. S., Verma, A., Owens, R. J., McDonough, M. A., Walsh, T. R., Schofield, C. J. & Spencer, J., Jan 2019, In : FEBS Journal. 286, 1, p. 169-183 15 p.

Research output: Contribution to journalArticle (Academic Journal)

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

Cyclic boronates as versatile scaffolds for KPC-2 β-lactamase inhibition

Tooke, C. L., Hinchliffe, P., Kranjnc, A., Mulholland, A. J., Brem, J., Schofield, C. J. & Spencer, J., 10 Jan 2020, In : Medicinal Chemistry. 6 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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76 Downloads (Pure)

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)

Detecting RNA base methylations in single cells by in situ hybridization

Ranasinghe, R. T., Challand, M. R., Ganzinger, K. A., Lewis, B. W., Softley, C., Schmied, W. H., Horrocks, M. H., Shivji, N., Chin, J. W., Spencer, J. & Klenerman, D., 13 Mar 2018, In : Nature Communications. 9, 1, 10 p., 655.

Research output: Contribution to journalArticle (Academic Journal)

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

Discovery of New and Potent InhA Inhibitors as Anti-tuberculosis Agents: Structure Based Virtual Screening Validated by Biological Assays and X-ray Crystallography

Kamsri, P., Hanwarinroj, C., Phusi, N., Pornprom, T., Chayajarus, K., Punkvang, A., Suttipanta, N., Srimanote, P., Suttisintong, K., Songsiriritthigul, C., Saparpakorn, P., Hannongbua, S., Rattanabunyong, S., Seetaha, S., Choowongkomon, K., Sureram, S., Kittakoop, P., Hongmanee, P., Santanirand, P., Chen, Z. & 7 others, Zhu, W., Blood, R. A., Takebayashi, Y., Hinchliffe, P., Mulholland, A. J., Spencer, J. & Pungpo, P., 27 Jan 2020, In : Journal of Chemical Information and Modeling. 60 (2020), 1, p. 226-234 9 p.

Research output: Contribution to journalArticle (Academic Journal)

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)

Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug

Evans, L. E., Krishna, A., Ma, Y., Webb, T. E., Marshall, D. C., Tooke, C. L., Spencer, J., Clarke, T. B., Armstrong, A. & Edwards, A. M., 9 May 2019, In : Journal of Medicinal Chemistry. 62, 9, p. 4411-4425 15 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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3 Citations (Scopus)
236 Downloads (Pure)

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)

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)

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)

In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors

Cain, R., Brem, J., Zollman, D., McDonough, M. A., Johnson, R. M., Spencer, J., Makena, A., Abboud, M. I., Cahill, S., Lee, S. Y., McHugh, P. J., Schofield, C. J. & Fishwick, C. W. G., 8 Feb 2018, In : Journal of Medicinal Chemistry. 61, 3, p. 1255-1260 6 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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20 Citations (Scopus)
213 Downloads (Pure)

In silico study directed towards identification of the key structural features of GyrB inhibitors targeting MTB DNA gyrase: HQSAR, CoMSIA and molecular dynamics simulations

Kamsri, P., Punkvang, A., Hannongbua, S., Suttisintong, K., Kittakoop, P., Spencer, J., Mulholland, A. J. & Pungpo, P., 2 Nov 2019, In : SAR and QSAR in Environmental Research. 30, 11, p. 775-800 27 p.

Research output: Contribution to journalArticle (Academic Journal)

3 Citations (Scopus)

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)

Mechanistic Insights into β-Lactamase-Catalysed Carbapenem Degradation Through Product Characterisation

Lohans, C. T., Freeman, E. I., Groesen, E. V., Tooke, C. L., Hinchliffe, P., Spencer, J., Brem, J. & Schofield, C. J., 20 Sep 2019, In : Scientific Reports. 9, 9 p., 13608.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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3 Citations (Scopus)
114 Downloads (Pure)

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)

Mixing and Matching Genes of Marine and Terrestrial Origin in the Biosynthesis of the Mupirocin Antibiotics

Wang, L., Song, Z., Race, P. R., Spencer, J., Simpson, T. J., Crump, M. P. & Willis, C. L., 9 May 2020, In : Chemical Science. 11, p. 5221-5226 6 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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10 Downloads (Pure)

Molecular Basis of Class A β-lactamase Inhibition by Relebactam

Tooke, C., Hinchliffe, P., Pauline, L., Mulholland, A., Brem, J., Schofield, C. J. & Spencer, J., 5 Aug 2019, In : Antimicrobial Agents and Chemotherapy. 49 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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142 Downloads (Pure)

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)

Multiscale simulations of clavulanate inhibition identify the reactive complex in class A β-lactamases and predict efficiency of inhibition

Fritz, R., Alzate-Morales, J. H., Spencer, J., Mulholland, A. J. & Van Der Kamp, M. W., 29 May 2018, In : Biochemistry. 4 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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7 Citations (Scopus)
170 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)

Non-Hydrolytic β-Lactam Antibiotic Fragmentation by l,d-Transpeptidases and Serine β-Lactamase Cysteine Variants

Lohans, C. T., Chan, H. T. H., Malla, T. R., Kumar, K., Kamps, J. J. A. G., McArdle, D. J. B., van Groesen, E., de Munnik, M., Tooke, C. L., Spencer, J., Paton, R. S., Brem, J. & Schofield, C. J., 11 Feb 2019, In : Angewandte Chemie - International Edition. 58, 7, p. 1990-1994 5 p.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
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4 Citations (Scopus)
210 Downloads (Pure)

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)

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)

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)