@article{84211,
  keywords = {Models, Molecular, Protein Conformation, Crystallography, X-Ray, Humans, Macromolecular Substances, Cryoelectron Microscopy, Carbon-Nitrogen Ligases, Protein Multimerization},
  author = {Eric Lynch and Derrick Hicks and Matthew Shepherd and James Endrizzi and Allison Maker and Jesse Hansen and Rachael Barry and Zemer Gitai and Enoch Baldwin and Justin Kollman},
  title = {Human CTP synthase filament structure reveals the active enzyme conformation},
  abstract = {<p>The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTPS activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments.</p>
},
  year = {2017},
  journal = {Nat Struct Mol Biol},
  volume = {24},
  pages = {507-514},
  month = {06/2017},
  issn = {1545-9985},
  doi = {10.1038/nsmb.3407},
  language = {eng},
}