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4iv64iv6
4iv6 is an enzyme Mycobacterium tuberculosis which get his structure analyzed by Baugh et al. [1] with other enzymes homologue in order to fight Mycobacterium tuberculosis relative infections. Function4iv6 functions were not studied and only structural infos are disponible. Nevertheless we can consider datas from other E.C.1.3.8.1[2] which came from other organisms. E.C.1.3.8.1[3] is communly found in following pathways with various functions: Valine Leucine and isoleucine pathways:[8]
Primary and Secondary structure[1]Isovaleryl-CoA dehydrogenase is the assembly of each composed of two chains and . Each of the two chains A and B are composed of 388 amino acids. An asymmetric unit is therefore composed of 776 amino acids and has a molecular weight of 86233.70 Da. 1% of the unit's amino acid have incomplete sidechains, which means that there are 11 missing residue in the assymetric unit.[2] The A chain is made up of (involving 221 residues) and (61 residues). Chain B is formed of (involving 218 residues) and (62 residues). Tertiary structuresThe two chains A and B of the isovaleryl-CoA dehydrogenase are linked by a (Dihydroflavine-Adenine Dinucleotide also known as FADH2 ). The protein is a tetramer, the surface between the two monomers of a single dimer of an acyl-CoA dehydrogenase contains the FAD binding sites and has extensive bonding interactions. There are 2 active sites in the tetramer, each of these 2 sites contains a FAD molecule and an acyl-CoA substrate binding site. [3] Enzymatic reaction[4][5][6]Enzyme accepted name: Short-chain acyl-CoA dehydrogenase Other names:Butanoyl-CoA dehydrogenase, Butyryl dehydrogenase, Short-chain acyl CoA dehydrogenase, Unsatured acyl-CoA reductase. Enzyme class: E.C.1.3.8.1[9] Substrate: A short-chain acyl CoA Prosthetic group: 1 electron-transfer flavoprotein such as FDA, for every Subunits Products: a short-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein Informed Pathways: Fatty acid degradation The enzyme from beef liver can accept acyl-chain lengths from 3 to 8 carbon atoms. From different organism the range can vary so we ignore if Mycobacterium tuberculosis gets the same lengths resolution. The highest activity reported for beef liver enzyme was for substrates with 4 and 5 carbon acyl-chain lengths. 4IV6 as a research tool4iv6 which belong to Mycobacterium tuberculosis was studied with other protein homolog. They were chosen to be studied as potential TB-Drugs target Studies have been made on homolog similarities aimed on their active site because with the knowledges of many homolog active site structure and how they work, we can design a inhibitor of those enzyme which can stop essential reaction and reduce or stop Mycobacterium tuberculosis infection. This strategy is called an « Homolog-rescue strategy ». This strategy can be generalized for other drug target for other diseases.
Structural highlights summary
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ReferencesReferences
- ↑ http://www.rcsb.org/structure/4IV6
- ↑ https://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4iv6
- ↑ https://en.wikipedia.org/wiki/Flavin_adenine_dinucleotide
- ↑ http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=4iv6
- ↑ https://www.ebi.ac.uk/intenz/query?cmd=SearchEC&ec=1.3.8.1
- ↑ https://enzyme.expasy.org/EC/1.3.8.1