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首页> 外文期刊>Acta crystallographica. Section D, Structural biology. >Novel mode of inhibition by D-tagatose 6-phosphate through a Heyns rearrangement in the active site of transaldolase B variants
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Novel mode of inhibition by D-tagatose 6-phosphate through a Heyns rearrangement in the active site of transaldolase B variants

机译：小说模式的抑制D-tagatose 6-phosphate通过海恩重排的活性部位transaldolase B变种

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摘要

B (TalB) and d-fructose-6-phosphate aldolase A (FSAA) from Escherichia coli are C-C bond-forming enzymes. Using kinetic inhibition studies and mass spectrometry, it is shown that enzyme variants of FSAA and TalB that exhibit D-fructose-6-phosphate aldolase activity are inhibited covalently and irreversibly by D-tagatose 6-phosphate (D-T6P), whereas no inhibition was observed for wild-type transaldolase B from E. coli. The crystal structure of the variant TalB(F178Y) with bound sugar phosphate was solved to a resolution of 1.46 angstrom and revealed a novel mode of covalent inhibition. The sugar is bound covalently via its C2 atom to the "epsilon-NH2 group of the active-site residue Lys132. It is neither bound in the open-chain form nor as the closed-ring form of D-T6P, but has been converted to beta-D-galactofuranose 6-phosphate (D-G6P), a five-membered ring structure. The furanose ring of the covalent adduct is formed via a Heyns rearrangement and subsequent hemiacetal formation. This reaction is facilitated by Tyr178, which is proposed to act as acid-base catalyst. The crystal structure of the inhibitor complex is compared with the structure of the Schiff-base intermediate of TalB(E96Q) formed with the substrate D-fructose 6-phosphate determined to a resolution of 2.20 angstrom. This comparison highlights the differences in stereochemistry at the C4 atom of the ligand as an essential determinant for the formation of the inhibitor adduct in the active site of the enzyme.
机译：B (TalB)和d-fructose-6-phosphate醛缩酶碳碳bond-forming (FSAA)大肠杆菌酶。质谱分析,结果表明,酶变异的FSAA和TalB展览D-fructose-6-phosphate醛缩酶活动抑制共价和不可逆转的D-tagatose 6-phosphate (D-T6P),而没有观察抑制野生型从大肠杆菌transaldolase B。结构变体TalB (F178Y)糖磷酸的决议来解决1.46埃,揭示了小说的模式共价抑制。“epsilon-NH2共价原子通过C2集团Lys132活性部位的残渣。既不绑定的开链形式,也不作为闭合环路的D-T6P形式,但已经形成到beta-D-galactofuranose 6-phosphate (D-G6P)五元环结构。通过海恩共价加合物的形成重排和随后的半缩醛形成。Tyr178,提出作为酸碱催化剂。比较复杂的结构席夫碱TalB (E96Q)形成的中间衬底果糖6-phosphate决心2.20埃的决议。比较突出的差异立体化学的C4原子配位体一个重要的决定因素的形成抑制剂加合物的活性部位酶。

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