Literature summary for 4.1.1.11 extracted from

Monteiro, D.C.F.; Patel, V.; Bartlett, C.P.; Nozaki, S.; Grant, T.D.; Gowdy, J.A.; Thompson, G.S.; Kalverda, A.P.; Snell, E.H.; Niki, H.; Pearson, A.R.; Webb, M.E.
The structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme A (2015), Chem. Biol., 22, 492-503 .

Activating Compound

Activating Compound	Comment	Organism	Structure
CoA	NMR spectroscopy demonstrates that CoA is an absolute requirement for PanD-PanZ complex formation, the binding site for AcCoA is very close to the protein-protein interface. PanZ promotes the activation of the zymogen of PanD to form aspartate alpha-decarboxylase (ADC) in a CoA-dependent manner	Escherichia coli
PanZ	structure of the complex of PanD and its activating factor PanZ, overview. Binding of AcCoA to PanZ is required to form the PanZ/PanD interface. PanZ-AcCoA activates PanD via selection of a reactive conformation of PanD. PanZ is essential for activation of the zymogen PanD to form the mature enzyme in vivo, and its deletion leads to beta-alanine auxotrophy. NMR spectroscopy demonstrates that CoA is an absolute requirement for PanD-PanZ complex formation. PanZ inhibits catalytic activity by activated PanD. Structural basis for activation, overview	Escherichia coli

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant protein complex PanD-PanZ-AcCoA, protein complexes are prepared with a 10:11 ratio of PanD to PanZ at a total protein concentration of 9-11 mg/ml, and a 2fold molar excess (with respect to PanZ) of acetyl-CoA. Crystals are obtained in 20% w/v PEG 3350, 0.1 M Bis-Tris propane, pH 7.4, and 0.2 M potassium thiocyanate, X-ray diffraction structure determination and analysis at 1.6 A resolution	Escherichia coli

Crystallization (Comment)

Organism

purified recombinant protein complex PanD-PanZ-AcCoA, protein complexes are prepared with a 10:11 ratio of PanD to PanZ at a total protein concentration of 9-11 mg/ml, and a 2fold molar excess (with respect to PanZ) of acetyl-CoA. Crystals are obtained in 20% w/v PEG 3350, 0.1 M Bis-Tris propane, pH 7.4, and 0.2 M potassium thiocyanate, X-ray diffraction structure determination and analysis at 1.6 A resolution

Escherichia coli

Protein Variants

Protein Variants	Comment	Organism
T57V	site-directed mutagenesis, an inactivatable PanD mutant	Escherichia coli

Inhibitors

Inhibitors	Comment	Organism	Structure
CoA	the CoA-dependent interaction inhibits catalysis by the activated enzyme. Binding of acetyl-CoA to PanZ is required to form the PanZ/PanD interface. PanZ.AcCoA inhibits the activated enzyme regulating pantothenate biosynthesis. The binding site for AcCoA is very close to the protein-protein interface. Structure of the complex of PanD and its activating factor PanZ with bound CoA, overview	Escherichia coli
PanZ	structure of the complex of PanD and its activating factor PanZ, overview. Binding of acetyl-CoA to PanZ is required to form the PanZ/PanD interface. PanZ-AcCoA activates PanD via selection of a reactive conformation of PanD. PanZ is essential for activation of the zymogen PanD to form the mature enzyme in vivo, and its deletion leads to beta-alanine auxotrophy. NMR spectroscopy dmonstrates that CoA is an absolute requirement for PanD-PanZ complex formation. PanZ inhibits catalytic activity by activated PanD	Escherichia coli

Organism

Organism	UniProt	Comment	Textmining
Escherichia coli	-	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
proteolytic modification	PanZ promotes the activation of the zymogen of PanD to form aspartate alpha-decarboxylase (ADC) in a CoA-dependent manner. Binding of PanZ promotes PanD processing, catalytic mechanism, detailed overview. Before binding of PanZ, the carbonyl of Gly24 forms a hydrogen bond to the side chain of Thr57. Binding of PanZ induces a conformation change in the peptide chain rotating the carbonyl of Gly24 to hydrogen bond to Tyr58 and shifting the hydroxyl of Ser25 to a position where reaction is possible. Following attack of the Ser25 hydroxyl on the carbonyl of Gly24 to form the oxyoxazolidine intermediate III, the side chain of Thr57 donates a proton to facilitate cleavage of the C-N bond to form the ester intermediate IV. The deprotonated Thr57 residue is then able to remove the a proton from Ser25 to cleave the peptide chain and generate a dehydroalanine residue V, which hydrolyzes to form the active enzyme	Escherichia coli

Synonyms

Synonyms	Comment	Organism
ADC	-	Escherichia coli
PanD	-	Escherichia coli

Cofactor

Cofactor	Comment	Organism	Structure
pyruvoyl cofactor	dependent on	Escherichia coli

General Information

General Information	Comment	Organism
malfunction	protein PanZ is essential for activation of the zymogen PanD to form ADC in vivo, and its deletion leads to beta-alanine auxotrophy	Escherichia coli
metabolism	the structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme A, regulatory model whereby the mature enzyme activity is limited and regulated by the concentration of CoA in the cell. Inhibition of mature enzyme catalysis reveals a second global role for PanZ in regulation of pantothenate biosynthesis. Such inhibitory activity is actually the primary metabolic role of PanZ, although the activation is also clearly essential	Escherichia coli
additional information	NMR analysis of the PanD-PanZ-AcCoA complex	Escherichia coli
physiological function	the enzyme is involved in the regulation of pantothenate biosynthesis	Escherichia coli