5LOT

Crystal structure of SCP2 thiolase from Leishmania mexicana. Complex of the C123A mutant with acetyl-CoA.

5LOT の概要

• エントリーDOI: 10.2210/pdb5lot/pdb
• 分子名称: 3-ketoacyl-CoA thiolase-like protein, ACETYL COENZYME *A (3 entities in total)
• 機能のキーワード: leishmania mexicana, scp2-thiolase, acetoacetyl-coa, lipid metabolism, transferase
• 由来する生物種: Leishmania mexicana (strain MHOM/GT/2001/U1103)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 199332.42

構造登録者

Harijan, R.K.,Kiema, T.-R.,Wierenga, R.K. (登録日: 2016-08-09, 公開日: 2017-01-18, 最終更新日: 2024-01-10)

主引用文献

Harijan, R.K.,Kiema, T.R.,Syed, S.M.,Qadir, I.,Mazet, M.,Bringaud, F.,Michels, P.A.M.,Wierenga, R.K.
Crystallographic substrate binding studies of Leishmania mexicana SCP2-thiolase (type-2): unique features of oxyanion hole-1.
Protein Eng. Des. Sel., 30:225-233, 2017

PubMed Abstract: Structures of the C123A variant of the dimeric Leishmania mexicana SCP2-thiolase (type-2) (Lm-thiolase), complexed with acetyl-CoA and acetoacetyl-CoA, respectively, are reported. The catalytic site of thiolase contains two oxyanion holes, OAH1 and OAH2, which are important for catalysis. The two structures reveal for the first time the hydrogen bond interactions of the CoA-thioester oxygen atom of the substrate with the hydrogen bond donors of OAH1 of a CHH-thiolase. The amino acid sequence fingerprints ( xS, EAF, G P) of three catalytic loops identify the active site geometry of the well-studied CNH-thiolases, whereas SCP2-thiolases (type-1, type-2) are classified as CHH-thiolases, having as corresponding fingerprints xS, DCF and G P. In all thiolases, OAH2 is formed by the main chain NH groups of two catalytic loops. In the well-studied CNH-thiolases, OAH1 is formed by a water (of the Wat-Asn(NEAF) dyad) and NE2 (of the GHP-histidine). In the two described liganded Lm-thiolase structures, it is seen that in this CHH-thiolase, OAH1 is formed by NE2 of His338 (HDCF) and His388 (GHP). Analysis of the OAH1 hydrogen bond networks suggests that the GHP-histidine is doubly protonated and positively charged in these complexes, whereas the HDCF histidine is neutral and singly protonated.

PubMed: 28062645
DOI: 10.1093/protein/gzw080

実験手法

X-RAY DIFFRACTION (2.25 Å)