Sandbox Reserved 321: Difference between revisions

The enzyme InhA is coded from the INHA gene that is similar in sequence to the ''[http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium]''gene which plays a role in [http://en.wikipedia.org/wiki/Fatty_acid_synthesis fatty acid synthesis], and is part of a short chain dehydrogenase/reductase family<ref name ="making drugs for inhA">Sacchettini, James (New Rochelle, NY) 1999 INHA crystals and three dimensional structure United States Albert Einstein College of Medicine of Yeshiva University (Bronx, NY) 5882878 http://www.freepatentsonline.com/5882878.html</ref><ref name ="phosphorylation of inhA">PMID:21143326</ref>. Inha is an [http://en.wikipedia.org/wiki/NADH NADH] dependent trans enoyl-acyl ACP carrier protein that is part of the fatty acid biosynthesis system: fatty acid synthase two (FASII), and plays a role in the synthesis of [http://en.wikipedia.org/wiki/Mycolic_acid Mycolic Acid]<ref name ="mech of thioamide drug action">PMID:17227913</ref><ref name ="phosphorylation of inhA">PMID:21143326</ref>. Mycolic acids are long chain fatty acids (C54 to C63) that are essential in cell wall formation of the human pathogen ''[http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]''as well as other mycobateria such as ''[http://en.wikipedia.org/wiki/Mycobacterium_leprae Mycobacterium leprae]'', and are associated with virulence<ref name ="TB">PMID2568869:</ref>. InhA has been proposed as the target of the [http://en.wikipedia.org/wiki/Thioamidedrugs thioamide] drugs, ethionamide (ETH)  and protionamide (PTH), which have been used in treatment of mycobacterial infections <ref name ="phosphorylation of inhA">PMID:21143326</ref>. However stains of ''M. tuberculosis that are resistant to thioamide drugs have been increaseing worldwide, and therefor research into the exact mechanisms of these drugs is of importance. 

The InhA enzyme <scene name='Sandbox_Reserved_321/Structural_progresion/1'>(go to original scene)</scene> of ''M. tuberculosis'' is a homotetramer composed of a repeating subunit of a single domain with a [http://en.wikipedia.org/wiki/Rossmann_fold Rossmann Fold] in the core that provides a NADH binding site<ref name ="crystallographic studies"/>.  The single domain can be broken down into two substructures that are connected by short peptide loop<ref name ="making drugs for inhA"/><ref name ="crystallographic studies">PMID:17588773</ref>.  The overall structure exhibits α/β folding wirh a series of α helices flanking a central β sheet of multiple parallel β strands<ref name ="crystallographic studies"/>.