2jug

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2jug

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Multienzyme Docking in Hybrid Megasynthetases

OverviewOverview

Hybrid multienzyme systems composed of polyketide synthase (PKS) and, nonribosomal polypeptide synthetase (NRPS) modules direct the biosynthesis, of clinically valuable natural products in bacteria. The fidelity of this, process depends on specific recognition between successive polypeptides in, each assembly line-interactions that are mediated by terminal 'docking, domains'. We have identified a new family of N-terminal docking domains, exemplified by TubCdd from the tubulysin system of Angiococcus disciformis, An d48. TubCdd is homodimeric, which suggests that NRPS subunits in mixed, systems self-associate to interact with partner PKS homodimers. The NMR, structure of TubCdd reveals a new fold featuring an exposed beta-hairpin, that serves as the binding site for the C-terminal docking domain of the, partner polypeptide. The pattern of charged residues on the contact, surface of the beta-hairpin is a key determinant of the interaction and, seems to constitute a 'docking code' that can be used to alter binding, affinity.

About this StructureAbout this Structure

2JUG is a Single protein structure of sequence from Angiococcus disciformis. Full crystallographic information is available from OCA.

ReferenceReference

Multienzyme docking in hybrid megasynthetases., Richter CD, Nietlispach D, Broadhurst RW, Weissman KJ, Nat Chem Biol. 2008 Jan;4(1):75-81. Epub 2007 Dec 9. PMID:18066054

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