Publication Date:
2002-12-03
Description:
Cellular communication in the nervous system is mediated by chemical messengers that include amino acids, monoamines, peptide hormones, and lipids. An interesting question is how neurons regulate signals that are transmitted by membrane-embedded lipids. Here, we report the 2.8 angstrom crystal structure of the integral membrane protein fatty acid amide hydrolase (FAAH), an enzyme that degrades members of the endocannabinoid class of signaling lipids and terminates their activity. The structure of FAAH complexed with an arachidonyl inhibitor reveals how a set of discrete structural alterations allows this enzyme, in contrast to soluble hydrolases of the same family, to integrate into cell membranes and establish direct access to the bilayer from its active site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bracey, Michael H -- Hanson, Michael A -- Masuda, Kim R -- Stevens, Raymond C -- Cravatt, Benjamin F -- R01 DA013173/DA/NIDA NIH HHS/ -- R01 DA013173-02/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 29;298(5599):1793-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12459591" target="_blank"〉PubMed〈/a〉
Keywords:
Amidohydrolases/antagonists & inhibitors/*chemistry/metabolism
;
Animals
;
Arachidonic Acids/metabolism
;
*Bacterial Proteins
;
Binding Sites
;
Cannabinoid Receptor Modulators
;
Catalysis
;
Catalytic Domain
;
Cell Membrane/*enzymology
;
Crystallography, X-Ray
;
Dimerization
;
Endocannabinoids
;
Helix-Turn-Helix Motifs
;
Lipid Bilayers
;
Models, Molecular
;
Organophosphonates/metabolism
;
Protein Conformation
;
Protein Folding
;
Protein Structure, Quaternary
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Rats
;
Recombinant Proteins/chemistry/metabolism
;
Signal Transduction
;
Solubility
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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