MetaCyc Polypeptide: PanD proenzyme, π protein

Gene: panD Accession Numbers: EG11747 (MetaCyc), b0131, ECK0130

Species: Escherichia coli K-12 substr. MG1655

Alternative forms of PanD proenzyme, π protein:
PanD α cleavage product (summary available)
PanD β cleavage product (summary available)

Aspartate 1-decarboxylase is responsible for the synthesis of β-alanine, which is needed in the biosynthesis of pantothenate. This enzyme is one of a small class of enzymes that use a covalently bound pyruvoyl prosthetic group. The pyruvoyl group is thought to act analogously to a pyridoxal phosphate cofactor by forming a Schiff base with the amino group of the substrate and then serving as an electron sink to facilitate the decarboxylation [vanPoelje90].

Pyruvoyl-containing enzymes are expressed as a zymogen which is processed post-translationally by a self-maturation cleavage called serinolysis. E. coli contains two more such enzymes, phosphatidylserine decarboxylase and adenosylmethionine decarboxylase.

The PanD proenzyme (π protein) is processed at the serine residue at position 25, resulting in two subunits, α and β, which form a complex that is enzymatically active. Autocatalytic processing of purified enzyme preparations occurs slowly at room temperature or 37° C, and at a higher rate at elevated temperatures [Ramjee97]. An ester intermediate at Ser25, formed by an N->O acyl shift, facilitates autoproteolysis [Albert98]. β-elimination of the ester results in proteolysis and the formation of dehydroalanine, which undergoes hydrolysis to form the pyruvoyl group [Schmitzberger03]. Experiments in E. coli [Nozaki12] and Salmonella enterica [Stuecker12] have now shown that PanZ is a maturation factor that triggers cleavage of pro-PanD to its mature and active form.

An S25A mutation eliminates self-cleavage of the π protein and eliminates enzymatic activity. A strain containing this mutant form of PanD absolutely requires exogenous β-alanine for growth [Kennedy04].

A crystal structure of aspartate 1-decarboxylase has been solved, identifying the ester intermediate of the autoproteolytic cleavage reaction. The active sites are located between the subunits [Albert98]. The Tyr58 residue may act as the proton donor in the reprotonation step of the decarboxylase reaction [Saldanha01]. Crystal structures of the unprocessed precursor as well as several point mutants reveal conformational constraints of the autoproteolysis reaction; a mechanism for self-processing has been proposed [Schmitzberger03].

panD mutants are auxotrophic for pantothenate or β-alanine [Cronan82, Merkel96]. Removal of β-alanine from the growth media of a panD mutant leads to depletion of coenzyme A [Jackowski83].

PanD: "pantothenate"

Reviews: [vanPoelje90, Perler98]

Locations: cytosol

Map Position: [146,314 <- 146,694]

Molecular Weight of Polypeptide: 13.834 kD (from nucleotide sequence)

pI: 6.11

Unification Links: ASAP:ABE-0000459 , CGSC:425 , EchoBASE:EB1697 , EcoGene:EG11747 , EcoliWiki:B0131 , EcoO157Cyc:PAND-MONOMER , ModBase:P0A790 , OU-Microarray:b0131 , PortEco:panD , PR:PRO_000023490 , Pride:P0A790 , Protein Model Portal:P0A790 , RefSeq:NP_414673 , RegulonDB:EG11747 , SMR:P0A790 , String:511145.b0131 , UniProt:P0A790

Relationship Links: InterPro:IN-FAMILY:IPR003190 , InterPro:IN-FAMILY:IPR009010 , Panther:IN-FAMILY:PTHR21012 , PDB:Structure:1AW8 , PDB:Structure:1PPY , PDB:Structure:1PQE , PDB:Structure:1PQF , PDB:Structure:1PQH , PDB:Structure:1PT0 , PDB:Structure:1PT1 , PDB:Structure:1PYQ , PDB:Structure:1PYU , PDB:Structure:3TM7 , PDB:Structure:4AOK , PDB:Structure:4AON , PDB:Structure:4AZD , Pfam:IN-FAMILY:PF02261 , ProDom:IN-FAMILY:PD009294

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0016540 - protein autoprocessing Inferred from experiment [Ramjee97]
GO:0006523 - alanine biosynthetic process Inferred by computational analysis [GOA01]
GO:0015940 - pantothenate biosynthetic process Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA06]
Molecular Function: GO:0004068 - aspartate 1-decarboxylase activity Inferred by computational analysis [GOA06, GOA01a, GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
GO:0016831 - carboxy-lyase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Ishihama08]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, GOA06]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers Coenzyme A and its modification

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

Sequence Features

Feature Class Location Common Name Citations Comment
Chain 1 -> 24  
UniProt: Aspartate 1-decarboxylase beta chain;
Chain 1 -> 24 β-subunit
Pyruvic-acid-Modification 25  
UniProt: Pyruvic acid (Ser).
Active-Site 25  
UniProt: Schiff-base intermediate with substrate; via pyruvic acid.
Chain 25 -> 126  
UniProt: Aspartate 1-decarboxylase alpha chain;
Modified-Residue 25 pyruvoyl cofactor
Chain 25 -> 126 α-subunit
Amino-Acid-Sites-That-Bind 57  
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Active-Site 58  
UniProt: Proton donor.
Protein-Segment 73 -> 75  
UniProt: Substrate binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 107  
[Fujita94, UniProt10a]
UniProt: (in Ref. 2);
Sequence-Conflict 120 -> 121  
[Fujita94, UniProt10a]
UniProt: (in Ref. 2);

10/20/97 Gene b0131 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11747; confirmed by SwissProt match.


Albert98: Albert A, Dhanaraj V, Genschel U, Khan G, Ramjee MK, Pulido R, Sibanda BL, von Delft F, Witty M, Blundell TL, Smith AG, Abell C (1998). "Crystal structure of aspartate decarboxylase at 2.2 A resolution provides evidence for an ester in protein self-processing." Nat Struct Biol 5(4);289-93. PMID: 9546220

Cronan82: Cronan JE, Littel KJ, Jackowski S (1982). "Genetic and biochemical analyses of pantothenate biosynthesis in Escherichia coli and Salmonella typhimurium." J Bacteriol 149(3);916-22. PMID: 7037743

Fujita94: Fujita N, Mori H, Yura T, Ishihama A (1994). "Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region." Nucleic Acids Res 22(9);1637-9. PMID: 8202364

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jackowski83: Jackowski S, Rock CO (1983). "Ratio of active to inactive forms of acyl carrier protein in Escherichia coli." J Biol Chem 258(24);15186-91. PMID: 6317688

Kennedy04: Kennedy J, Kealey JT (2004). "Tools for metabolic engineering in Escherichia coli: inactivation of panD by a point mutation." Anal Biochem 327(1);91-6. PMID: 15033515

Merkel96: Merkel WK, Nichols BP (1996). "Characterization and sequence of the Escherichia coli panBCD gene cluster." FEMS Microbiol Lett 143(2-3);247-52. PMID: 8837478

Nozaki12: Nozaki S, Webb ME, Niki H (2012). "An activator for pyruvoyl-dependent l-aspartate α-decarboxylase is conserved in a small group of the γ-proteobacteria including Escherichia coli." Microbiologyopen 1(3);298-310. PMID: 23170229

Perler98: Perler FB (1998). "Breaking up is easy with esters." Nat Struct Biol 5(4);249-52. PMID: 9546209

Ramjee97: Ramjee MK, Genschel U, Abell C, Smith AG (1997). "Escherichia coli L-aspartate-alpha-decarboxylase: preprotein processing and observation of reaction intermediates by electrospray mass spectrometry." Biochem J 323 ( Pt 3);661-9. PMID: 9169598

Saldanha01: Saldanha SA, Birch LM, Webb ME, Nabbs BK, von Delft F, Smith AG, Abell C (2001). "Identification of Tyr58 as the proton donor in the aspartate-alpha-decarboxylase reaction." Chem Commun (Camb) NIL(18);1760-1. PMID: 12240302

Schmitzberger03: Schmitzberger F, Kilkenny ML, Lobley CM, Webb ME, Vinkovic M, Matak-Vinkovic D, Witty M, Chirgadze DY, Smith AG, Abell C, Blundell TL (2003). "Structural constraints on protein self-processing in L-aspartate-alpha-decarboxylase." EMBO J 22(23);6193-204. PMID: 14633979

Stuecker12: Stuecker TN, Hodge KM, Escalante-Semerena JC (2012). "The missing link in coenzyme A biosynthesis: PanM (formerly YhhK), a yeast GCN5 acetyltransferase homologue triggers aspartate decarboxylase (PanD) maturation in Salmonella enterica." Mol Microbiol 84(4);608-19. PMID: 22497218

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

vanPoelje90: van Poelje PD, Snell EE (1990). "Pyruvoyl-dependent enzymes." Annu Rev Biochem 59;29-59. PMID: 2197977

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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