Crystal structure of a D-amino acid aminotransferase: how the protein controls stereoselectivity.
Crystal structure of a D-amino acid aminotransferase: how the protein controls stereoselectivity.
复制标题
D-氨基酸转氨酶的晶体结构：蛋白质如何控制立体选择性。
DOI：
10.1021/bi00030a002
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Ringe,D
中科院分区：
文献类型：
--
作者：
Sugio,S;Petsko,GA;Manning,JM;Soda,K;Ringe,D
摘要：用结晶学方法测定了磷酸吡哆胺形式的D-氨基酸氨基转移酶(d-AAT)的三维结构。这种含有磷酸吡哆醛(PLP)的酶的折叠与任何其他利用PLP作为其机制的一部分且其结构已知的酶完全不同。然而，d-AAT的活性部位与相应的转氨酶L-氨基酸L-天冬氨酸氨基转移酶有一些惊人的相似之处。这些相似之处代表着在PLP辅因子上实施转氨基化学的问题的共同解决方案的收敛进化。讨论了这些相似性在转氨化反应中间体稳定中的可能作用。此外，d-AAT与支链L氨基酸转氨酶的序列相似性表明，后者也将具有与d-AAT相似的折叠。细菌除L-氨基酸转氨酶外，还具有仅能转氨D-氨基酸的酶(Soda&Esaki，1985)。这种酶对细菌很重要，因为它催化细菌细胞壁的基本成分D-谷氨酸和D-丙氨酸的合成，以及各种其他D-氨基酸的合成。因此，D-氨基酸氨基转移酶(d-AAT)1是开发新型抗菌剂的靶酶
Revised Manuscript Received May 18, 1995® abstract: The three-dimensional structure of D-amino acid aminotransferase (d-AAT) in the pyridoxamine phosphate form has beendetermined crystallographically. The fold of this pyridoxal phosphate (PLP)-containing enzyme is completely different from those of any of the other enzymes that utilize PLP as part of their mechanism and whose structures are known. However, there are some striking similarities between the active sites of d-AAT and the corresponding enzyme that transaminates L-amino acids, L-aspartate aminotransferase. These similarities represent convergent evolution to a common solution of the problem of enforcing transamination chemistry on the PLP cofactor. Implications of these similarities are discussed in terms of their possible roles in the stabilization of intermediates of a transamination reaction. In addition, sequence similarity between d-AAT and branched chain L-amino acid aminotransferase suggests that this latter enzyme will also have a fold similar to that of d-AAT.Bacteria have, in addition to L-amino acid aminotrans-ferases, an enzyme capable of transaminating only D-amino acids (Soda & Esaki, 1985). The enzyme is important for bacteria because it catalyzes the syntheses of D-glutamic acid and D-alanine, which are essential constituents of the bacterial cell wall, and a wide variety of other D-amino acids as well. As a consequence, D-amino acid aminotransferase (d-AAT) 1 is a target enzyme for the development of novel antimicrobial