墨西哥利什曼原虫scp2 -硫酶(2型)的晶体学底物结合研究:氧阴离子孔-1的独特特征

R. Harijan, T. Kiema, Shahan M Syed, Imran Qadir, M. Mazet, F. Bringaud, P. Michels, R. Wierenga
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引用次数: 7

摘要

报道了墨西哥利什曼原虫二聚体scp2 -硫酶(2型)(m-硫酶)的C123A变体的结构,分别与乙酰辅酶a和乙酰乙酰辅酶a络合。巯基酶的催化位点含有OAH1和OAH2两个氧阴离子空穴,对催化具有重要作用。这两种结构首次揭示了底物coa -硫酯氧原子与chh -硫酶OAH1的氢键供体之间的氢键相互作用。三个催化环的氨基酸序列指纹图谱(xS、EAF、gp)识别了cnh -硫酶的活性位点几何形状,而scp2 -硫酶(1型、2型)被归类为chh -硫酶,对应的指纹图谱为xS、DCF和gp。在所有硫酶中,OAH2由两个催化环的主链NH基团形成。在被充分研究的cnh硫酶中,OAH1是由water - asn (NEAF)二联体的水和ghp -组氨酸的NE2形成的。在描述的两种配体lm -硫酶结构中,可以看到在chh -硫酶中,OAH1是由His338 (HDCF)和His388 (GHP)的NE2形成的。对OAH1氢键网络的分析表明,在这些复合物中,ghp组氨酸是双质子化的,带正电荷,而HDCF组氨酸是中性的,单质子化的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Crystallographic substrate binding studies of Leishmania mexicana SCP2-thiolase (type-2): unique features of oxyanion hole-1
C 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.
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