This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3f5o

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 18:16, 25 December 2014

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

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.
Ligands:	, , ,
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[THEM2_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).^[1] ^[2]

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^[3]

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

References

↑ Cheng Z, Song F, Shan X, Wei Z, Wang Y, Dunaway-Mariano D, Gong W. Crystal structure of human thioesterase superfamily member 2. Biochem Biophys Res Commun. 2006 Oct 13;349(1):172-7. Epub 2006 Aug 14. PMID:16934754 doi:10.1016/j.bbrc.2006.08.025
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3f5o"

Categories: Homo sapiens | Gong, W | Xu, H | Hotdog fold | Hydrolase

@@ Line 6: / Line 6: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3f5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f5o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f5o RCSB], [http://www.ebi.ac.uk/pdbsum/3f5o PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/THEM2_HUMAN THEM2_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).<ref>PMID:16934754</ref> <ref>PMID:19170545</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3f5o

From Proteopedia

Revision as of 18:16, 25 December 2014

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox