a structural study of this mysterious polymerase
Well Khosla’s group have done it again. In this months Nature Structural Biology is the crystal structure of actinorhodin KS-CLF. For most of you this’ll mean absolutely nothing to you but save to say its one of the major enzyme complexes I’ve been investigating as part of my PhD and our groups (particularly Matt Crumps) have been trying to solve the structure as well (Southhampton Katy had Crystals which were diffracting to a low resolution months ago – but then had a car accident which has left most of it shelved whilst she recouperated)
The structure is heterodimeric (NOT a dimer of heterodimer as we’ve predicted in the past based on gel filtration and ultracentrifugation studies) – and it is structurally very similar to the KAS enzymes of type II fatty acid biosynthesis (no surprise there) – it does raise a few difficult questions for my old thesis – and I’ll have to sit down and think about what the paper actually means.
As with all Khosla papers though it throws up a few points which you just have to raise an eyebrow or two at – the obsession with including MCAT in polyketide biosynthesis, the sweeping statement that CLF is NOT responsible for decarboxylation of malonate to acetate (and the subsequent lack of explanation of what they think this 400 odd amino acid enzyme actually does all day) – despite mutagenesis and chemical modifiction data to the contrary, and finally an image of ACP bound to CLF during chain elongation.