Crystal Structure of 3-Amino-5-hydroxybenzoic Acid (AHBA) Synthase
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- 作者：Janina C. Eads ; Morgan Beeby ; Giovanna Scapin ; Tin-Wein Yu ; and Heinz G. Floss
- 刊名：Biochemistry
- 出版年：1999
- 出版时间：August 3, 1999
- 年：1999
- 卷：38
- 期：31
- 页码：9840 - 9849
- 全文大小：304K
- 年卷期：v.38,no.31(August 3, 1999)
- ISSN：1520-4995
文摘
The biosynthesis of ansamycin antibiotics, including rifamycin B, involves the synthesis ofan aromatic precursor, 3-amino-5-hydroxybenzoic acid (AHBA), which serves as starter for the assemblyof the antibiotics' polyketide backbone. The terminal enzyme of AHBA formation, AHBA synthase, is adimeric, pyridoxal 5'-phosphate (PLP) dependent enzyme with pronounced sequence homology to a numberof PLP enzymes involved in the biosynthesis of antibiotic sugar moieties. The structure of AHBA synthasefrom Amycolatopsis mediterranei has been determined to 2.0 Å resolution, with bound cofactor, PLP,and in a complex with PLP and an inhibitor (gabaculine). The overall fold of AHBA synthase is similarto that of the aspartate aminotransferase family of PLP-dependent enzymes, with a large domain containinga seven-stranded 
-sheet surrounded by 
-helices and a smaller domain consisting of a four-strandedantiparallel -sheet and four -helices. The uninhibited form of the enzyme shows the cofactor covalentlylinked to Lys188 in an internal aldimine linkage. On binding the inhibitor, gabaculine, the internal aldiminelinkage is broken, and a covalent bond is observed between the cofactor and inhibitor. The active site iscomposed of residues from two subunits of AHBA synthase, indicating that AHBA synthase is active asa dimer.
-sheet surrounded by -helices and a smaller domain consisting of a four-strandedantiparallel -sheet and four -helices. The uninhibited form of the enzyme shows the cofactor covalentlylinked to Lys188 in an internal aldimine linkage. On binding the inhibitor, gabaculine, the internal aldiminelinkage is broken, and a covalent bond is observed between the cofactor and inhibitor. The active site iscomposed of residues from two subunits of AHBA synthase, indicating that AHBA synthase is active asa dimer.