PDBsum entry 4cs0

Lyase

PDB id: 4cs0

Contents

Protein chains

127 a.a.

127 a.a.

Ligands

SCN

ACO

Metals

_MG

Waters ×62

References listed in PDB file

Key reference

• Title: The structure of the pand/panz protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme a.
• Authors: D.C.Monteiro, V.Patel, C.P.Bartlett, S.Nozaki, T.D.Grant, J.A.Gowdy, G.S.Thompson, A.P.Kalverda, E.H.Snell, H.Niki, A.R.Pearson, M.E.Webb.
• Ref.: Chem Biol, 2015, 22, 492-503. [DOI no: 10.1016/j.chembiol.2015.03.017]
• PubMed id: 25910242

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 α-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.