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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The crystal structure of AjiA1 reveals a novel structural motion mechanism in the adenylate-forming enzyme family

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Author(s):
de Paiva, Fernanda C. R. [1] ; Chan, Karen [2] ; Samborskyy, Markiyan [2] ; Silber, Ariel M. [3] ; Leadlay, Peter F. [2] ; Dias, Marcio V. B. [4, 1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci 2, Dept Microbiol, Sao Paulo - Brazil
[2] Univ Cambridge, Dept Biochem, Cambridge - England
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, LaBTryps Lab Biochem Tryps, Sao Paulo - Brazil
[4] Univ Warwick, Dept Chem, Coventry, W Midlands - England
Total Affiliations: 4
Document type: Journal article
Source: ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY; v. 76, n. 12, p. 1201-1210, DEC 1 2020.
Web of Science Citations: 0
Abstract

Adenylate-forming enzymes (AFEs) are a mechanistic superfamily of proteins that are involved in many cellular roles. In the biosynthesis of benzoxazole antibiotics, an AFE has been reported to play a key role in the condensation of cyclic molecules. In the biosynthetic gene cluster for the benzoxazole AJI9561, AjiA1 catalyzes the condensation of two 3-hydroxyanthranilic acid (3-HAA) molecules using ATP as a co-substrate. Here, the enzymatic activity of AjiA1 is reported together with a structural analysis of its apo form. The structure of AjiA1 was solved at 2.0 angstrom resolution and shows a conserved fold with other AFE family members. AjiA1 exhibits activity in the presence of 3-HAA (K-m = 77.86 +/- 28.36, k(cat) = 0.04 +/- 0.004) and also with the alternative substrate 3-hydroxybenzoic acid (3-HBA; K-m = 22.12 +/- 31.35, k(cat) = 0.08 +/- 0.005). The structure of AjiA1 in the apo form also reveals crucial conformational changes that occur during the catalytic cycle of this enzyme which have not been described for any other AFE member. Consequently, the results shown here provide insights into this protein family and a new subgroup is proposed for enzymes that are involved in benzoxazole-ring formation. (AU)

FAPESP's process: 16/06034-2 - The biological role of amino acids and their metabolites in Trypanosoma cruzi
Grantee:Ariel Mariano Silber
Support type: Research Projects - Thematic Grants
FAPESP's process: 18/00351-1 - Applied structural biology involved in the biosynthesis of natural products: biotechnolgical aplications and study of unusual molecular reactions
Grantee:Marcio Vinicius Bertacine Dias
Support type: Regular Research Grants