2JUG

Multienzyme Docking in Hybrid Megasynthetases

Summary for 2JUG

• Entry DOI: 10.2210/pdb2jug/pdb
• NMR Information: BMRB: 15442
• Descriptor: TubC protein (1 entity in total)
• Functional Keywords: docking domain, dimer, nonribosomal peptide synthetase, tubulysin, ligase, phosphopantetheine, biosynthetic protein
• Biological source: Angiococcus disciformis
• Total number of polymer chains: 2
• Total formula weight: 16252.74

Authors

Richter, C.D.,Nietlispach, D.,Broadhurst, R.W.,Weissman, K.J. (deposition date: 2007-08-24, release date: 2007-12-11, Last modification date: 2024-05-29)

Primary citation

Richter, C.D.,Nietlispach, D.,Broadhurst, R.W.,Weissman, K.J.
Multienzyme docking in hybrid megasynthetases
Nat.Chem.Biol., 4:75-81, 2008

PubMed Abstract: 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.

PubMed: 18066054
DOI: 10.1038/nchembio.2007.61

Experimental method

SOLUTION NMR