Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes
Fatty acid amide hydrolase (FAAH) is a well-characterized member of the amidase signature (AS) family of serine hydrolases. The membrane-bound FAAH protein is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide, that regulate a wide range of mammali...
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MDPI AG
2019-09-01
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| author | Cho-Ah Min Ji-Sook Yun Eun Hwa Choi Ui Wook Hwang Dong-Hyung Cho Je-Hyun Yoon Jeong Ho Chang |
| author_facet | Cho-Ah Min Ji-Sook Yun Eun Hwa Choi Ui Wook Hwang Dong-Hyung Cho Je-Hyun Yoon Jeong Ho Chang |
| author_sort | Cho-Ah Min |
| collection | DOAJ |
| description | Fatty acid amide hydrolase (FAAH) is a well-characterized member of the amidase signature (AS) family of serine hydrolases. The membrane-bound FAAH protein is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide, that regulate a wide range of mammalian behaviors, including pain perception, inflammation, sleep, and cognitive/emotional state. To date, limited crystal structures of FAAH and non-mammalian AS family proteins have been determined and used for structure-based inhibitor design. In order to provide broader structural information, the crystal structure of FAAH from the pathogenic fungus <i>Candida albicans</i> was determined at a resolution of 2.2 Å. A structural comparison with a brown rat <i>Rattus norvegicus</i> FAAH as well as with other bacterial AS family members, MAE2 and PAM, showed overall similarities but there were several discriminative regions found: the transmembrane domain and the hydrophobic cap of the brown rat FAAH were completely absent in the fungal FAAH structure. Along with these results, a phylogenetic analysis of 19 species within the AS family showed that fungal FAAHs diverged from a common ancestor before the separation of eukarya and prokarya. Taken together, this study provides insights into developing more potent inhibitors of FAAH as well as expanding our knowledge of the relationships between AS family members. |
| first_indexed | 2024-04-14T02:22:46Z |
| format | Article |
| id | doaj.art-1a108fc155054c92b6b8b373f7d2ce7b |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-04-14T02:22:46Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-1a108fc155054c92b6b8b373f7d2ce7b2022-12-22T02:17:59ZengMDPI AGCrystals2073-43522019-09-019947210.3390/cryst9090472cryst9090472Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family EnzymesCho-Ah Min0Ji-Sook Yun1Eun Hwa Choi2Ui Wook Hwang3Dong-Hyung Cho4Je-Hyun Yoon5Jeong Ho Chang6Department of Biology Education, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology Education, Kyungpook National University, Daegu 41566, KoreaResearch Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu 41566, KoreaDepartment of Biology Education, Kyungpook National University, Daegu 41566, KoreaSchool of Life Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Biology Education, Kyungpook National University, Daegu 41566, KoreaFatty acid amide hydrolase (FAAH) is a well-characterized member of the amidase signature (AS) family of serine hydrolases. The membrane-bound FAAH protein is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide, that regulate a wide range of mammalian behaviors, including pain perception, inflammation, sleep, and cognitive/emotional state. To date, limited crystal structures of FAAH and non-mammalian AS family proteins have been determined and used for structure-based inhibitor design. In order to provide broader structural information, the crystal structure of FAAH from the pathogenic fungus <i>Candida albicans</i> was determined at a resolution of 2.2 Å. A structural comparison with a brown rat <i>Rattus norvegicus</i> FAAH as well as with other bacterial AS family members, MAE2 and PAM, showed overall similarities but there were several discriminative regions found: the transmembrane domain and the hydrophobic cap of the brown rat FAAH were completely absent in the fungal FAAH structure. Along with these results, a phylogenetic analysis of 19 species within the AS family showed that fungal FAAHs diverged from a common ancestor before the separation of eukarya and prokarya. Taken together, this study provides insights into developing more potent inhibitors of FAAH as well as expanding our knowledge of the relationships between AS family members.https://www.mdpi.com/2073-4352/9/9/472fatty acid amide hydrolaseAS familyFAAH inhibitorMAE2PAM |
| spellingShingle | Cho-Ah Min Ji-Sook Yun Eun Hwa Choi Ui Wook Hwang Dong-Hyung Cho Je-Hyun Yoon Jeong Ho Chang Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes Crystals fatty acid amide hydrolase AS family FAAH inhibitor MAE2 PAM |
| title | Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes |
| title_full | Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes |
| title_fullStr | Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes |
| title_full_unstemmed | Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes |
| title_short | Comparison of <i>Candida Albicans</i> Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes |
| title_sort | comparison of i candida albicans i fatty acid amide hydrolase structure with homologous amidase signature family enzymes |
| topic | fatty acid amide hydrolase AS family FAAH inhibitor MAE2 PAM |
| url | https://www.mdpi.com/2073-4352/9/9/472 |
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