底物和抑制剂结合位点棒状杆菌glutamicum diaminopimelate脱氢酶。
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高Scapin G, Cirilli M, Reddy SG, Y, Vederas JC,布兰查德JS
底物和抑制剂结合位点棒状杆菌glutamicum diaminopimelate脱氢酶。
生物化学。1998年3月10日,37 (10):3278 - 85。
- PubMed ID
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9521647 (在PubMed]
- 文摘
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棒状杆菌属的三维结构glutamicum diaminopimelate脱氢酶作为二进制与基质复杂meso-diaminopimelate (meso-DAP)和三元复合辅酶ii +和isoxazoline抑制剂(方丈金丝Lane-Bell, P。Kanwar, P.S.S.Vederas, j . c (1994) j。化学。Soc。116年,6513 - 6520年)已经解决和改进对2.2 x射线衍射数据。Diaminopimelate脱氢酶为大约35000分子量亚基,是唯一的脱氢酶存在于细菌Diaminopimelate /赖氨酸生物合成途径。赖氨酸生物合成的酶的抑制剂已经被提议作为潜在的抗生素或除草剂,因为哺乳动物缺乏这方面的代谢途径。Diaminopimelate脱氢酶催化的,可逆的,吡啶dinucleotide-dependent氧化脱氨基作用的分子酸异构中心meso-diaminopimelate生成L-2-amino-6-oxopimelate。内消旋酶绝对是特定的立体异构体的弹跳,必须区分两种截然相反的手性氨基酸中心在同一对称的衬底。酶的三维结构的测定——meso-diaminopimelate允许分子基础的描述复杂的立体定向歧视。 The substrate is bound in an elongated cavity, in which the distribution of residues that act as hydrogen bond donors or acceptors defines a single orientation in which the substrate may bind in order to position the D-amino acid center of meso-DAP near the oxidized nucleotide. The previously described isoxazoline inhibitor binds at the same site as DAP but has its L-amino acid center positioned where the D-amino acid center of meso-DAP would normally be located, thereby generating a nonproductive inhibitor complex. The relative positions of the N-terminal dinucleotide and C-terminal substrate-binding domains in the diaminopimelate dehydrogenase--NADP+, diaminopimelate dehydrogenase--DAP, and diaminopimelate dehydrogenase--NADP(+)--inhibitor complexes confirm our previous observations that the enzyme undergoes significant conformational changes upon binding of both dinucleotide and substrate.