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磷酸吡哆醛对胸苷酸合成酶的抑制作用。

Inhibition of thymidylate synthase by pyridoxal phosphate.

作者信息

Chen S C, Daron H H, Aull J L

机构信息

Department of Chemistry, Auburn University, AL 36849.

出版信息

Int J Biochem. 1989;21(11):1217-21. doi: 10.1016/0020-711x(89)90006-2.

DOI:10.1016/0020-711x(89)90006-2
PMID:2515076
Abstract
  1. Pyridoxal phosphate (PLP) reversibly inhibited thymidylate synthase from Lactobacillus casei with a KI of 0.6-0.9 microM. 2. The inhibition was competitive with dUMP and noncompetitive with 5,10-methylenetetrahydrofolate which is consistent with an ordered addition of substrates. 3. The spectrum of PLP was altered by the addition of thymidylate synthase. The spectral changes suggest formation of a thiohemiacetal with an enzyme sulfhydryl group rather than Schiff base formation with a lysine side chain.
摘要
  1. 磷酸吡哆醛（PLP）可逆性抑制干酪乳杆菌的胸苷酸合成酶，抑制常数（KI）为0.6 - 0.9微摩尔。2. 这种抑制作用对脱氧尿苷一磷酸（dUMP）具有竞争性，对5,10 - 亚甲基四氢叶酸是非竞争性的，这与底物的有序添加一致。3. 添加胸苷酸合成酶后，PLP的光谱发生了改变。光谱变化表明与酶的巯基形成了硫代半缩醛，而不是与赖氨酸侧链形成席夫碱。

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1
Inhibition of thymidylate synthase by pyridoxal phosphate.磷酸吡哆醛对胸苷酸合成酶的抑制作用。
Int J Biochem. 1989;21(11):1217-21. doi: 10.1016/0020-711x(89)90006-2.
2
Inhibition of thymidylate synthase by glyceraldehyde 3-phosphate.3-磷酸甘油醛对胸苷酸合成酶的抑制作用。
Int J Biochem. 1991;23(7-8):733-6. doi: 10.1016/0020-711x(91)90045-o.
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Interaction of 5-ethynyl-2'-deoxyuridylate with thymidylate synthetase.5-乙炔基-2'-脱氧尿苷酸与胸苷酸合成酶的相互作用。
J Med Chem. 1981 Dec;24(12):1537-40. doi: 10.1021/jm00144a036.
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Interaction of thymidylate synthase with pyridoxal 5'-phosphate as studied by UV/visible difference spectroscopy and molecular modeling.
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Interaction of pyridoxal phosphate with thymidylate synthase: spectral and equilibrium dialysis studies.
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Isolation of a covalent steady-state intermediate in glutamate 60 mutants of thymidylate synthase.
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Aspartate 221 of thymidylate synthase is involved in folate cofactor binding and in catalysis.胸苷酸合成酶的天冬氨酸221参与叶酸辅因子结合及催化过程。
Biochemistry. 1998 Jun 23;37(25):9038-42. doi: 10.1021/bi9802770.
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5-Cyano-2'-deoxyuridine 5'-phosphate: a potent competitive inhibitor of thymidylate synthetase.
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Reversible inhibition by pyridoxal 5'-phosphate and irreversible inactivation by urea and guanidine hydrochloride of thymidylate synthase from Lactobacillus leichmannii.
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