3f5o

From Proteopedia

Crystal Structure of hTHEM2(undecan-2-one-CoA) complex

PDB ID 3f5o

Drag the structure with the mouse to rotate

Structural highlights

3f5o is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACO13_HUMAN Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. Has acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates. Can also hydrolyze 3-hydroxyphenylacetyl-CoA and 3,4-dihydroxyphenylacetyl-CoA (in vitro). May play a role in controlling adaptive thermogenesis (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The focus of this paper is the hotdog-fold thioesterase THEM2 from human (hTHEM2; Swiss-Prot entry Q9NPJ3 ). In an earlier communication (Cheng, Z., Song, F., Shan, X., Wei, Z., Wang, Y., Dunaway-Mariano, D., and Gong, W. (2006) Crystal structure of human thioesterase superfamily member 2, Biochem. Biophys. Res. Commun. 349, 172-177) we reported the apo crystal structure of hTHEM2. Herein, we report the results of an extensive hTHEM2 substrate screen, the structure determination of hTHEM2 complexed with the inert substrate analogue undecan-2-one-CoA (in which OC-CH(2)-S substitutes for OC-S) and the kinetic analysis of active site mutants. The work described in this paper represents the first reported structure-function based analysis of a human hotdog-fold thioesterase. The catalytic mechanism proposed involves the Asp65/Ser83 assisted attack of a water molecule at the Gly57/Asn50 polarized thioester CO and the Asn50 assisted departure of the thiolate leaving group. Thioesterase activity was observed with acyl-CoAs but not with the human acyl-ACP or with an acyl-Cys peptide. The medium-to-long-chain fatty acyl-CoAs displayed the smallest K(m) values. The substrate specificity profile was analyzed within the context of the liganded enzyme to define the structural determinants of substrate recognition. Based on the results of this structure-function analysis we hypothesize that the physiological role of hTHEM2 involves catalysis of the hydrolysis of cytosolic medium-to-long-chain acyl-CoA thioesters.

The mechanisms of human hotdog-fold thioesterase 2 (hTHEM2) substrate recognition and catalysis illuminated by a structure and function based analysis.,Cao J, Xu H, Zhao H, Gong W, Dunaway-Mariano D Biochemistry. 2009 Feb 17;48(6):1293-304. PMID:19170545^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cao J, Xu H, Zhao H, Gong W, Dunaway-Mariano D. The mechanisms of human hotdog-fold thioesterase 2 (hTHEM2) substrate recognition and catalysis illuminated by a structure and function based analysis. Biochemistry. 2009 Feb 17;48(6):1293-304. PMID:19170545 doi:10.1021/bi801879z