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ORF 12 gene product N-terminal This is the N-terminal domain of Streptomyces clavuligerus ORF 12 gene product, which is directly involved in biosynthesis of Clavulanic acid (CA). The N-terminal domain consists of one four-stranded antiparallel beta-sheet surrounded by four alpha-helices and folds similarly to steroid isomerases and polyketide cyclases (PKTC). However, the N-terminal domain has no apparent polar-lined active-site pocket or conserved catalytic residues analogous to those of either the steroid isomerases or PKTCs. ORF 12 has 2 binding sites, CA is able to bind both to an active site and between the two domains. The active site pocket is lined by residues from both the N- and the C-terminal domains (His88, Ser173, Thr209, Ser234, Ser278, Met383, Phe374, Ala376 and Phe385). The C-2 carboxylate of CA is positioned deep in the pocket, making electrostatic interactions with Lys375, Arg418 and Lys89. Lys89 is located in strand beta-2 of the N-terminal domain and may also be involved in the beta-lactam core-binding region, including the residues Lys89 as well as Arg418. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",