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PMID: 9788915 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural basis for the inhibition of firefly luciferase by a general anesthetic.

Biophysical journal ·Vol. 75 ·No. 5 ·1998-11-00 ·Pages 2205-11

Franks NP, Jenkins A, Conti E, Lieb WR, Brick P

Abstract

The firefly luciferase enzyme from Photinus pyralis is probably the best-characterized model system for studying anesthetic-protein interactions. It binds a diverse range of general anesthetics over a large potency range, displays a sensitivity to anesthetics that is very similar to that found in animals, and has an anesthetic sensitivity that can be modulated by one of its substrates (ATP). In this paper we describe the properties of bromoform acting as a general anesthetic (in Rana temporaria tadpoles) and as an inhibitor of the firefly luciferase enzyme at high and low ATP concentrations. In addition, we describe the crystal structure of the low-ATP form of the luciferase enzyme in the presence of bromoform at 2.2-A resolution. These results provide a structural basis for understanding the anesthetic inhibition of the enzyme, as well as an explanation for the ATP modulation of its anesthetic sensitivity.

MeSH Terms
Adenosine Triphosphate/metabolism Anesthetics/pharmacology Animals Binding Sites/physiology Binding, Competitive Coleoptera/enzymology Crystallography, X-Ray Enzyme Inhibitors/pharmacology Firefly Luciferin/metabolism Hydrocarbons, Brominated/pharmacology Larva/drug effects Luciferases/chemistry Models, Molecular Peptide Synthases/chemistry Protein Conformation Ranidae/embryology Trihalomethanes
Chemicals
Anesthetics Enzyme Inhibitors Hydrocarbons, Brominated Trihalomethanes Firefly Luciferin Adenosine Triphosphate Luciferases Peptide Synthases bromoform
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Franks N P
Biophysics Section, The Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, England. n.franks@ic.ac.uk
Jenkins A
Conti E
Lieb W R
Brick P
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(98)77664-7
Email
n.franks@ic.ac.uk
Published
1998-11-00
Pages
2205-11
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1299894
Subset
IM
External Links
PubMed source DOI: 10.1016/S0006-3495(98)77664-7 PMC Full Text View journal details
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