Characterization of a Novel Ser-cisSer-Lys Catalytic Triad in Comparison with the Classical Ser-His-Asp Triad

Shin, Sang Yong; Yun, Yeoung‐Sang; Koo, Hyun; Kim, Yu Sam; Choi, Kwan Yong; Oh, Byung Ha

doi:10.1074/jbc.m302156200

Cited by 59 publications

(54 citation statements)

References 33 publications

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“…In contrast to Toc64-III and mtOM64, AMIl does not contain tetratricopeptide repeat (TPR) motifs in its C-terminal domain. Toc64-III and mtOM64 do not contain the essential residues of the supposed anúdase catalytic triad (Lys-c¿,sSer-Ser; Shin et al 2003;Bracey et al 2002) as pin-pointed in Fig. la (for AMIl: K36, S113, and S137).…”

Section: Discussionmentioning

confidence: 99%

Subcellular localization and tissue specific expression of amidase 1 from Arabidopsis thaliana

Pollmann

Neu

Lehmann

et al. 2006

Planta

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Amidase 1 (AMIl) from Arabidopsis thaliana converts indole-3-acetamide (IAM), into indole-3-acetic acid (IAA). AMIl is part of a small isogene family comprising seven members in A. thaliana encoding proteins which share a conserved glycine-and serinerich amidase-signature. One member of this family has been characterized as an iV-acylethanolamine-cleaving fatty acid amidohydrolase (FAAH) and two other members are part of the preprotein translocon of the outer envelope of chloroplasts (Toe complex) or mitochondria (Tom complex) and presumably lack enzymatic activity. Among the hitherto characterized proteins of this family, AMIl is the only member with indole-3-acetamide hydrolase activity, and IAM is the preferred substrate while iV-acylethanolamines and oleamide are not hydrolyzed significantly, thus suggesting a role of AMIl in auxin biosynthesis. Whereas the enzymatic function of AMIl has been determined in vitro, the subcellular localization of the enzyme remained unclear. By using different GFP-fusion construets and an A. thaliana transient expression system,

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Section: Discussionmentioning

confidence: 99%

Subcellular localization and tissue specific expression of amidase 1 from Arabidopsis thaliana

Pollmann

Neu

Lehmann

et al. 2006

Planta

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“…AS enzymes possess an unusual serine-serine-lysine catalytic triad, which functions to promote amide bond hydrolysis in a manner generally analogous to the serine-histidine-aspartic acid triad more commonly observed in serine hydrolases (27,28). X-ray crystallography studies have revealed that FAAH possesses multiple modes for membrane binding, including a hydrophobic plateau domain for monotopic integration that resides adjacent to the active site and appears to grant the enzyme access to bilayerembedded fatty acid amide substrates (29).…”

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confidence: 99%

A Second Fatty Acid Amide Hydrolase with Variable Distribution among Placental Mammals

Wei

Mikkelsen

McKinney

et al. 2006

Journal of Biological Chemistry

311

281

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Fatty acid amides constitute a large and diverse class of lipid transmitters that includes the endogenous cannabinoid anandamide and the sleep-inducing substance oleamide. The magnitude and duration of fatty acid amide signaling are controlled by enzymatic hydrolysis in vivo. Fatty acid amide hydrolase (FAAH) activity in mammals has been primarily attributed to a single integral membrane enzyme of the amidase signature (AS) family. Here, we report the functional proteomic discovery of a second membrane-associated AS enzyme in humans that displays FAAH activity. The gene that encodes this second FAAH enzyme was found in multiple primate genomes, marsupials, and more distantly related vertebrates, but, remarkably, not in a number of lower placental mammals, including mouse and rat. The two human FAAH enzymes, which share 20% sequence identity and are referred to hereafter as FAAH-1 and FAAH-2, hydrolyzed primary fatty acid amide substrates (e.g. oleamide) at equivalent rates, whereas FAAH-1 exhibited much greater activity with N-acyl ethanolamines (e.g. anandamide) and N-acyl taurines. Both enzymes were sensitive to the principal classes of FAAH inhibitors synthesized to date, including O-aryl carbamates and ␣-keto heterocycles. These data coupled with the overlapping, but distinct tissue distributions of FAAH-1 and FAAH-2 suggest that these proteins may collaborate to control fatty acid amide catabolism in primates. The apparent loss of the FAAH-2 gene in some lower mammals should be taken into consideration when extrapolating genetic or pharmacological findings on the fatty acid amide signaling system across species.The fatty acid amide family of bioactive lipids can be divided into at least three chemical classes: N-acylethanolamines (1) and modulates several neurobehavioral processes, including pain (4), feeding (5), and memory (6). Oleamide is a sleep-inducing lipid that accumulates in the cerebrospinal fluid of sleep-deprived animals (2, 7). Oleamide has been shown to affect several protein receptors, including serotonin (8), GABA (9, 10) and cannabinoid (11) receptors, as well as gap junctions (12), and at least a subset of these proteins appears to be critical for mediating the hypnotic effects of oleamide (13,14). NATs are representative members of a large family of N-acyl amino acids that vary in both acyl chain and amino acid content (3, 15-17). These lipids have been shown to modulate pain sensation (17) and activate TRP channels (16).The signaling function of fatty acid amides is terminated by enzymatic hydrolysis in vivo. A principal enzyme involved in this process is fatty acid amide hydrolase (FAAH) (18 -20). Mice with a targeted disruption in the FAAH gene (FAAH(Ϫ/Ϫ) mice) (21) or those treated with FAAH inhibitors (22, 23) are severely impaired in their ability to degrade fatty acid amides and show hypersensitivity to the pharmacological effects of these lipids. Blockade of FAAH activity also leads to highly elevated endogenous levels of fatty acid amides in the nervous system (21-23) and periph...

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“…This network of hydrogen bonds is close to an unusual cis peptide bond, between Ser217 and Gly216, which has been proposed to be essential for catalysis in other enzymes belonging to the AS family. 20 The subsequent nucleophilic attack produces 4 with effectively no barrier, indicating that TI formation and Ser241 deprotonation are concerted. Semiempirical methods, such as PM3, often overestimate barriers, 12 so higher level calculations (B3LYP/6-31+G(d)) were used to correct the reaction energies.…”

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confidence: 99%

QM/MM modelling of oleamide hydrolysis in fatty acid amide hydrolase (FAAH) reveals a new mechanism of nucleophile activation

et al. 2005

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Characterization of a Novel Ser-cisSer-Lys Catalytic Triad in Comparison with the Classical Ser-His-Asp Triad

Cited by 59 publications

References 33 publications

Subcellular localization and tissue specific expression of amidase 1 from Arabidopsis thaliana

Subcellular localization and tissue specific expression of amidase 1 from Arabidopsis thaliana

A Second Fatty Acid Amide Hydrolase with Variable Distribution among Placental Mammals

QM/MM modelling of oleamide hydrolysis in fatty acid amide hydrolase (FAAH) reveals a new mechanism of nucleophile activation

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