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Crystal Structure of NADPH-Dependent Methylglyoxal Reductase Gre2 from Candida Albicans
Open AccessArticle

Comparison of Candida Albicans Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes

1
Department of Biology Education, Kyungpook National University, Daegu 41566, Korea
2
Research Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu 41566, Korea
3
School of Life Sciences, Kyungpook National University, Daegu 41566, Korea
4
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Crystals 2019, 9(9), 472; https://doi.org/10.3390/cryst9090472
Received: 23 August 2019 / Revised: 5 September 2019 / Accepted: 8 September 2019 / Published: 10 September 2019
(This article belongs to the Special Issue Crystallographic Studies of 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 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 Candida albicans was determined at a resolution of 2.2 Å. A structural comparison with a brown rat Rattus norvegicus 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. View Full-Text
Keywords: fatty acid amide hydrolase; AS family; FAAH inhibitor; MAE2; PAM fatty acid amide hydrolase; AS family; FAAH inhibitor; MAE2; PAM
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Min, C.-A.; Yun, J.-S.; Choi, E.H.; Hwang, U.W.; Cho, D.-H.; Yoon, J.-H.; Chang, J.H. Comparison of Candida Albicans Fatty Acid Amide Hydrolase Structure with Homologous Amidase Signature Family Enzymes. Crystals 2019, 9, 472.

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