1AFW

THE 1.8 ANGSTROM CRYSTAL STRUCTURE OF THE DIMERIC PEROXISOMAL THIOLASE OF SACCHAROMYCES CEREVISIAE

1AFW の概要

• エントリーDOI: 10.2210/pdb1afw/pdb
• 分子名称: 3-KETOACETYL-COA THIOLASE, (4R)-2-METHYLPENTANE-2,4-DIOL (3 entities in total)
• 機能のキーワード: thiolase, fatty acid metabolism
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Peroxisome: P27796
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84388.51

構造登録者

Mathieu, M.,Wierenga, R.K. (登録日: 1997-03-15, 公開日: 1997-06-16, 最終更新日: 2024-02-07)

主引用文献

Mathieu, M.,Modis, Y.,Zeelen, J.P.,Engel, C.K.,Abagyan, R.A.,Ahlberg, A.,Rasmussen, B.,Lamzin, V.S.,Kunau, W.H.,Wierenga, R.K.
The 1.8 A crystal structure of the dimeric peroxisomal 3-ketoacyl-CoA thiolase of Saccharomyces cerevisiae: implications for substrate binding and reaction mechanism.
J.Mol.Biol., 273:714-728, 1997

PubMed Abstract: The dimeric, peroxisomal 3-ketoacyl-CoA thiolase catalyses the conversion of 3-ketoacyl-CoA into acyl-CoA, which is shorter by two carbon atoms. This reaction is the last step of the beta-oxidation pathway. The crystal structure of unliganded peroxisomal thiolase of the yeast Saccharomyces cerevisiae has been refined at 1.8 A resolution. An unusual feature of this structure is the presence of two helices, completely buried in the dimer and sandwiched between two beta-sheets. The analysis of the structure shows that the sequences of these helices are not hydrophobic, but generate two amphipathic helices. The helix in the N-terminal domain exposes the polar side-chains to a cavity at the dimer interface, filled with structured water molecules. The central helix in the C-terminal domain exposes its polar residues to an interior polar pocket. The refined structure has also been used to predict the mode of binding of the substrate molecule acetoacetyl-CoA, as well as the reaction mechanism. From previous studies it is known that Cys125, His375 and Cys403 are important catalytic residues. In the proposed model the acetoacetyl group fits near the two catalytic cysteine residues, such that the oxygen atoms point towards the protein interior. The distance between SG(Cys125) and C3(acetoacetyl-CoA) is 3.7 A. The O2 atom of the docked acetoacetyl group makes a hydrogen bond to N(Gly405), which would favour the formation of the covalent bond between SG(Cys125) and C3(acetoacetyl-CoA) of the intermediate complex of the two-step reaction. The CoA moiety is proposed to bind in a groove on the surface of the protein molecule. Most of the interactions of the CoA molecule are with atoms of the loop domain. The three phosphate groups of the CoA moiety are predicted to interact with side-chains of lysine and arginine residues, which are conserved in the dimeric thiolases.

PubMed: 9402066
DOI: 10.1006/jmbi.1997.1331

実験手法

X-RAY DIFFRACTION (1.8 Å)