α-Methylacyl-CoA racemase (AMACR), also known as P504S, is an enzyme that plays a vital role in branched-chain fatty acid metabolism. It catalyses the racemization of α-methyl-branched fatty acyl-CoAs, converting the (2S)-epimer to a near racemic mixture of the (2R)- and (2S)-epimers. In Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), α-methylacyl-CoA racemase is known as MCR (with 44% amino acid sequence identity with the human AMACR enzyme), and is of particular interest due to its involvement in cholesterol metabolism. Cholesterol is an essential component of the host cell membrane and represents a potential carbon and energy source for M. tuberculosis during infection. The enzyme enables the conversion of α-methyl-branched fatty acids derived from cholesterol metabolism into forms that can be utilized by M. tuberculosis for growth and persistence within the host, a key component of M. tuberculosis pathogenesis. Understanding the structure–function relationships of MCR in M. tuberculosis has implications for the development of novel therapeutic strategies against TB. Targeting MCR presents an attractive approach to disrupting the bacterium’s ability to utilize cholesterol and impair its survival within the host. Inhibiting MCR activity could potentially starve M. tuberculosis of essential nutrients, rendering it more susceptible to host immune responses and antimicrobial treatments. Furthermore, the structure–function relationships of MCR in M. tuberculosis can guide the development of selective inhibitors that specifically target the bacterium while sparing the human counterpart. Here you can see a crystal structure of the Alpha-Methylacyl-CoA racemase from Mycobacterium tuberculosis (PDB code: 8RP4)

Structure rendered with @proteinimaging , post-processed with @stylar.ai_official and depicted with @corelphotopaint

#molecularart ... #racemase ... #tuberculosis ... #xray .. #fattyacid