Fatty-acid amide hydrolase 1

Basic Information
Short Name	FAAH, FAAH1
UNP ID	P97612
Organism	Rattus norvegicus
Cys Site	Cys269
Family/Domain	Amidase family
Known Ligand	Ligand list
Function Type	Metabolic enzyme

Summary

Protein Function

Fatty acid amide hydrolase or FAAH (EC 3.5.1.99, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. FAAH is an integral membrane hydrolase with a single N-terminal transmembrane domain. In vitro, FAAH has esterase and amidase activity. In vivo, FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). (From Wikipedia)
Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates. (From Uniprot)

Cys Function & Property

Cys269 is close to the active sites of FAAH.

• Hydrophobic property:

• SASA:

Cys269: 13.878 A^2

Protein Sequence

MVLSEVWTTL SGVSGVCLAC SLLSAAVVLR WTGRQKARGA ATRARQKQRA
SLETMDKAVQ RFRLQNPDLD SEALLTLPLL QLVQKLQSGE LSPEAVFFTY
LGKAWEVNKG TNCVTSYLTD CETQLSQAPR QGLLYGVPVS LKECFSYKGH
DSTLGLSLNE GMPSESDCVV VQVLKLQGAV PFVHTNVPQS MLSFDCSNPL
FGQTMNPWKS SKSPGGSSGG EGALIGSGGS PLGLGTDIGG SIRFPSAFCG
ICGLKPTGNR LSKSGLKGCV YGQTAVQLSL GPMARDVESL ALCLKALLCE
HLFTLDPTVP PLPFREEVYR SSRPLRVGYY ETDNYTMPSP AMRRALIETK
QRLEAAGHTL IPFLPNNIPY ALEVLSAGGL FSDGGRSFLQ NFKGDFVDPC
LGDLILILRL PSWFKRLLSL LLKPLFPRLA AFLNSMRPRS AEKLWKLQHE
IEMYRQSVIA QWKAMNLDVL LTPMLGPALD LNTPGRATGA ISYTVLYNCL
DFPAGVVPVT TVTAEDDAQM ELYKGYFGDI WDIILKKAMK NSVGLPVAVQ
CVALPWQEEL CLRFMREVEQ LMTPQKQPS

Structural Information

• Known structure with covalent ligand:
  

4J5P

• Protein structure:

Related Pathway

• >ko04723 Retrograde endocannabinoid signaling <br/

Experimental Evidence

Cys-directed mutation, Homologous Analysis Of Sequence, Molecular Docking

Reference

1. Otrubova K, Cravatt B F, Boger D L. Design, synthesis, and characterization of α-ketoheterocycles that additionally target the cytosolic port Cys269 of fatty acid amide hydrolase[J]. Journal of medicinal chemistry, 2014, 57(3): 1079-1089. 24456116
   
2. Otrubova K, Brown M, McCormick M S, et al. Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues[J]. Journal of the American Chemical Society, 2013, 135(16): 6289-6299. 23581831