4CS0: Direct Visualisation Of Strain-induced Protein Post-translational Modification

Citation:
Abstract
Coenzyme A (CoA) is an ubiquitous and essential cofactor, synthesized from the precursor pantothenate. Vitamin biosynthetic pathways are normally tightly regulated, including the pathway from pantothenate to CoA. However, no regulation of pantothenate biosynthesis has been identified. We have recently described an additional component in the pantothenate biosynthetic pathway, PanZ, which promotes the activation of the zymogen, PanD, to form aspartate alpha-decarboxylase (ADC) in a CoA-dependent manner. Here we report the structure of PanZ in complex with PanD, which reveals the structural basis for the CoA dependence of this interaction and activation. In addition, we show that PanZ acts as a CoA-dependent inhibitor of ADC catalysis. This inhibitory effect can effectively regulate the biosynthetic pathway to pantothenate, and thereby also regulate CoA biosynthesis. This represents a previously unobserved mode of metabolic regulation whereby a cofactor-utilizing protein negatively regulates the biosynthesis of the same cofactor.
PDB ID: 4CS0Download
MMDB ID: 128027
PDB Deposition Date: 2014/3/2
Updated in MMDB: 2017/06
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 4CS0: octameric; determined by author and by software (PISA)
Molecular Components in 4CS0
Label Count Molecule
Proteins (8 molecules)
4
Aspartate 1-decarboxylase(Gene symbol: panD)
Molecule annotation
4
Panz(Gene symbol: panM)
Molecule annotation
Chemicals (12 molecules)
1
4
2
4
3
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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