Biomaterial Database

Structural basis for the inhibition of firefly luciferase by a general anesthetic. 1998

N P Franks, and A Jenkins, and E Conti, and W R Lieb, and P Brick

Biophysics Section, The Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, England. n.franks@ic.ac.uk

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.

UI	MeSH Term	Description	Entries
D007814	Larva	Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals.	Maggots,Tadpoles,Larvae,Maggot,Tadpole
D008156	Luciferases	Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.	Luciferase
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D010453	Peptide Synthases	Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.	Peptide Synthetases,Acid-Amino-Acid Ligases,Acid Amino Acid Ligases,Ligases, Acid-Amino-Acid,Synthases, Peptide,Synthetases, Peptide
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D011898	Ranidae	The family of true frogs of the order Anura. The family occurs worldwide except in Antarctica.	Frogs, True,Rana,Frog, True,True Frog,True Frogs
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006842	Hydrocarbons, Brominated	Hydrocarbon compounds with one or more HYDROGEN atoms substituted with BROMINE.	Brominated Hydrocarbons
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000777	Anesthetics	Agents capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general ANESTHESIA, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site.	Anesthetic,Anesthetic Agents,Anesthetic Drugs,Anesthetic Effect,Anesthetic Effects,Agents, Anesthetic,Drugs, Anesthetic,Effect, Anesthetic,Effects, Anesthetic