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Function

Primary and Secondary structure

Isovaleryl-CoA dehydrogenase is the assembly of two asymmetric units each composed of two chains and B linked by a ligand (Dihydroflavine-Adenine Dinucleotide). 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.

The A chain is made up of 17 helices (involving 221 residues) and 14 beta-sheets (61 residues).

Chain B is formed of 17 helices (involving 218 residues) and 14 beta-sheets (62 residues).

Tertiary structures

Enzymatic reaction

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[1]

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

Pathways: Fatty acid degradation

Other information:

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 M.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 tool

4iv6 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 M.tuberculosis infection. This strategy is called an « Homolog-rescue strategy ». This strategy can be generalized for other drug target for other diseases.

Structural highlights

 :Light Grey:1st sub-unit, Light green:2nd sub-unit, Blue and red:FDA

 : Red: helix alpha, Blue:FDA, Yellow: Beta sheet

 : Green: FDA, Purple: Polar region, Light grey: Hydrophobic region