4AE7

Crystal structure of human THEM5

Summary for 4AE7

• Entry DOI: 10.2210/pdb4ae7/pdb
• Related: 4AE8
• Descriptor: THIOESTERASE SUPERFAMILY MEMBER 5 (2 entities in total)
• Functional Keywords: hydrolase, hotdog-fold
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 24535.95

Authors

Zhuravleva, E.,Gut, H.,Hynx, D.,Marcellin, D.,Bleck, C.K.E.,Genoud, C.,Cron, P.,Keusch, J.J.,Dummler, B.,Degli Esposti, M.,Hemmings, B.A. (deposition date: 2012-01-09, release date: 2012-07-11, Last modification date: 2024-05-08)

Primary citation

Zhuravleva, E.,Gut, H.,Hynx, D.,Marcellin, D.,Bleck, C.K.E.,Genoud, C.,Cron, P.,Keusch, J.J.,Dummler, B.,Esposti, M.D.,Hemmings, B.A.
Acyl Coenzyme a Thioesterase Them5/Acot15 is Involved in Cardiolipin Remodeling and Fatty Liver Development.
Mol.Cell.Biol., 32:2685-, 2012

PubMed Abstract: Acyl coenzyme A (acyl-CoA) thioesterases hydrolyze thioester bonds in acyl-CoA metabolites. The majority of mammalian thioesterases are α/β-hydrolases and have been studied extensively. A second class of Hotdog-fold enzymes has been less well described. Here, we present a structural and functional analysis of a new mammalian mitochondrial thioesterase, Them5. Them5 and its paralog, Them4, adopt the classical Hotdog-fold structure and form homodimers in crystals. In vitro, Them5 shows strong thioesterase activity with long-chain acyl-CoAs. Loss of Them5 specifically alters the remodeling process of the mitochondrial phospholipid cardiolipin. Them5(-/-) mice show deregulation of lipid metabolism and the development of fatty liver, exacerbated by a high-fat diet. Consequently, mitochondrial morphology is affected, and functions such as respiration and β-oxidation are impaired. The novel mitochondrial acyl-CoA thioesterase Them5 has a critical and specific role in the cardiolipin remodeling process, connecting it to the development of fatty liver and related conditions.

PubMed: 22586271
DOI: 10.1128/MCB.00312-12

Experimental method

X-RAY DIFFRACTION (1.45 Å)