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Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase.
Biochemistry. 1999 Aug 03; 38(31):9840-9.B

Abstract

The biosynthesis of ansamycin antibiotics, including rifamycin B, involves the synthesis of an aromatic precursor, 3-amino-5-hydroxybenzoic acid (AHBA), which serves as starter for the assembly of the antibiotics' polyketide backbone. The terminal enzyme of AHBA formation, AHBA synthase, is a dimeric, pyridoxal 5'-phosphate (PLP) dependent enzyme with pronounced sequence homology to a number of PLP enzymes involved in the biosynthesis of antibiotic sugar moieties. The structure of AHBA synthase from Amycolatopsis mediterranei has been determined to 2.0 A resolution, with bound cofactor, PLP, and in a complex with PLP and an inhibitor (gabaculine). The overall fold of AHBA synthase is similar to that of the aspartate aminotransferase family of PLP-dependent enzymes, with a large domain containing a seven-stranded beta-sheet surrounded by alpha-helices and a smaller domain consisting of a four-stranded antiparallel beta-sheet and four alpha-helices. The uninhibited form of the enzyme shows the cofactor covalently linked to Lys188 in an internal aldimine linkage. On binding the inhibitor, gabaculine, the internal aldimine linkage is broken, and a covalent bond is observed between the cofactor and inhibitor. The active site is composed of residues from two subunits of AHBA synthase, indicating that AHBA synthase is active as a dimer.

Authors+Show Affiliations

School of Biochemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10433690

Citation

Eads, J C., et al. "Crystal Structure of 3-amino-5-hydroxybenzoic Acid (AHBA) Synthase." Biochemistry, vol. 38, no. 31, 1999, pp. 9840-9.
Eads JC, Beeby M, Scapin G, et al. Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase. Biochemistry. 1999;38(31):9840-9.
Eads, J. C., Beeby, M., Scapin, G., Yu, T. W., & Floss, H. G. (1999). Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase. Biochemistry, 38(31), 9840-9.
Eads JC, et al. Crystal Structure of 3-amino-5-hydroxybenzoic Acid (AHBA) Synthase. Biochemistry. 1999 Aug 3;38(31):9840-9. PubMed PMID: 10433690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase. AU - Eads,J C, AU - Beeby,M, AU - Scapin,G, AU - Yu,T W, AU - Floss,H G, PY - 1999/8/6/pubmed PY - 1999/8/6/medline PY - 1999/8/6/entrez SP - 9840 EP - 9 JF - Biochemistry JO - Biochemistry VL - 38 IS - 31 N2 - The biosynthesis of ansamycin antibiotics, including rifamycin B, involves the synthesis of an aromatic precursor, 3-amino-5-hydroxybenzoic acid (AHBA), which serves as starter for the assembly of the antibiotics' polyketide backbone. The terminal enzyme of AHBA formation, AHBA synthase, is a dimeric, pyridoxal 5'-phosphate (PLP) dependent enzyme with pronounced sequence homology to a number of PLP enzymes involved in the biosynthesis of antibiotic sugar moieties. The structure of AHBA synthase from Amycolatopsis mediterranei has been determined to 2.0 A resolution, with bound cofactor, PLP, and in a complex with PLP and an inhibitor (gabaculine). The overall fold of AHBA synthase is similar to that of the aspartate aminotransferase family of PLP-dependent enzymes, with a large domain containing a seven-stranded beta-sheet surrounded by alpha-helices and a smaller domain consisting of a four-stranded antiparallel beta-sheet and four alpha-helices. The uninhibited form of the enzyme shows the cofactor covalently linked to Lys188 in an internal aldimine linkage. On binding the inhibitor, gabaculine, the internal aldimine linkage is broken, and a covalent bond is observed between the cofactor and inhibitor. The active site is composed of residues from two subunits of AHBA synthase, indicating that AHBA synthase is active as a dimer. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/10433690/Crystal_structure_of_3_amino_5_hydroxybenzoic_acid__AHBA__synthase_ L2 - https://doi.org/10.1021/bi990018q DB - PRIME DP - Unbound Medicine ER -