Directed selective pressure on a β-lactamase to analyse molecular changes involved in development of enzyme function

ABSTRACT THE study of protein mutants has proved a powerful technique in the elucidation of structure–function relationships (see for example refs 1 and 2), but this approach has hardly been

used strategically in the investigation of enzyme mechanisms, though its potential for clarifying the role of individual amino acids and their effect on catalytic rates is obvious. We

report here the consequences of directed selective pressure on the plasmid-coded _β_-lactamase from _Escherichia coli_ RTEM. Selection for strains with increased resistance to cephalosporin

C has allowed the isolation of mutant enzymes whose catalytic properties are changed in the desired direction. Access through your institution Buy or subscribe This is a preview of

subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online access $199.00 per year only

$3.90 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout

ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS POSITIVE EPISTASIS DRIVES

CLAVULANIC ACID RESISTANCE IN DOUBLE MUTANT LIBRARIES OF BLAC Β-LACTAMASE Article Open access 17 February 2024 BETA-LACTAMASE DEPENDENT AND INDEPENDENT EVOLUTIONARY PATHS TO HIGH-LEVEL

AMPICILLIN RESISTANCE Article Open access 25 June 2024 MAPPING THE DETERMINANTS OF CATALYSIS AND SUBSTRATE SPECIFICITY OF THE ANTIBIOTIC RESISTANCE ENZYME CTX-M Β-LACTAMASE Article Open

access 12 January 2023 REFERENCES * Perutz, M. F., and Ten Eyck, L. F., _Cold Spring Harb. Symp. quant. Biol._, 36, 295–310 (1971). Article  CAS  Google Scholar  * Schmitz, A., Schmeissner,

U., Miller, J. H., and Lu, P., _J. biol. Chem._, 251, 3359–3366 (1976). CAS  PubMed  Google Scholar  * Knox, J. R., Kelly, J. A., Moews, P. C., and Murthy, N. S., _J. molec. Biol._, 104

865–875 (1976). Article  CAS  Google Scholar  * Wu, T. T., Lin, E. C. C., and Tanaka, S., _J. Bact._, 96 447–456 (1968). CAS  PubMed  Google Scholar  * Burleigh, B. D., Rigby, P. W., and

Hartley, B. S., _Biochem. J._, 143, 341–352 (1974). Article  CAS  Google Scholar  * Langridge, J., _Molec. gen. Genet._, 105, 74–83 (1969). Article  CAS  Google Scholar  * Betz, J. L.,

Brown, P. R., Smyth, M. J., and Clarke, P. H., _Nature_, 247, 261–264 (1974). Article  ADS  CAS  Google Scholar  * Wills, C., _Fedn Proc._, 35, 2098–2101 (1976). CAS  Google Scholar  *

Pollock, M. R., Fleming, J., and Petrie, S., _Proc. 2nd Fedn Mtg Eur. Biochem. Soc._, 139–152 (1967). * Hartley, C. L., Petrocheilov, V., and Richmond, M. H., _Nature_, 260, 558 (1976).

Article  ADS  CAS  Google Scholar  * Falkow, S., _Infectious Multiple Drug Resistance_ (Pion, London, 1975). Book  Google Scholar  * Curtius, N. A. C., Hughes, J. M., and Ross, G. W.,

_Antimicrob. Ag. Chemother._, 208–213 (1976). * Richmond, M. H., _Meth. Enzym._, 43, 86–100 (1975). Article  CAS  Google Scholar  * Melling, J., and Scott, G. K., _Biochem. J._, 130, 55–62

(1972). Article  CAS  Google Scholar  * Adelberg, E. A., Mandel, M., and Chen, G. C. C., _Biochem. biophys. Res. commun._, 18, 788–795 (1965). Article  CAS  Google Scholar  * Novick, R. P.,

_Biochem. J._, 83, 229–235 (1962). Article  CAS  Google Scholar  * Novick, R. P., _Biochem. J._, 83, 236–240 (1962). Article  CAS  Google Scholar  * Sykes, R. B., and Nordström, K.,

_Antimicrob. Ag. Chemother._, 94–99 (1972). * Samuni, A., _Analyt. Biochem._, 63, 17–26 (1975). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS

* Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, Massachusetts, 02138 ALAN HALL & JEREMY R. KNOWLES Authors * ALAN HALL View author publications You can also

search for this author inPubMed Google Scholar * JEREMY R. KNOWLES View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE HALL, A., KNOWLES, J. Directed selective pressure on a β-lactamase to analyse molecular changes involved in development of enzyme function.

_Nature_ 264, 803–804 (1976). https://doi.org/10.1038/264803a0 Download citation * Received: 07 September 1976 * Accepted: 27 October 1976 * Issue Date: 23 December 1976 * DOI:

https://doi.org/10.1038/264803a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently

available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative