Disease relevance of SCO6898

• Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis [1].
• To test this hypothesis, the carboxylase subunits were expressed in Escherichia coli and purified [2].
• This protein displays identity over a short stretch of amino acids with the recently discovered epsilon-subunits of Streptomyces coelicolor, suggesting that it might be an epsilon-subunit of the mycobacterial acyl-CoA carboxylase [2].

High impact information on SCO6898

• A biotin-dependent acyl-CoA carboxylase was purified from M. tuberculosis H37Rv by avidin affinity chromatography, and the three major protein components were determined by N-terminal sequencing to be the 63-kDa alpha3-subunit (AccA3, Rv3285), the 59-kDa beta5-subunit (AccD5, Rv3280), and the 56-kDa beta4-subunit (AccD4, Rv3799) [2].
• This epsilon-subunit contains five sets of tandem repeats at the N terminus that are required for maximal enhancement of carboxylase activity [2].
• Our findings enable bioengineering of the acyl-CoA carboxylase (ACCase) substrate specificity to provide novel extender units for the combinatorial biosynthesis of polyketides [3].

Chemical compound and disease context of SCO6898

• Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv [2].

References