|Gene:||panD||Accession Numbers: EG11747 (MetaCyc), b0131, ECK0130|
Species: Escherichia coli K-12 substr. MG1655
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 [Kennedy04a].
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].
|Map Position: [146,314 <- 146,694]|
Molecular Weight of Polypeptide: 13.834 kD (from nucleotide sequence)
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
|Biological Process:||GO:0016540 - protein autoprocessing
GO:0006523 - alanine biosynthetic process [GOA01a]
GO:0015940 - pantothenate biosynthetic process [UniProtGOA12, UniProtGOA11a, GOA06]
|Molecular Function:||GO:0004068 - aspartate 1-decarboxylase activity
[GOA06, GOA01, GOA01a]
GO:0016829 - lyase activity [UniProtGOA11a]
GO:0016831 - carboxy-lyase activity [UniProtGOA11a]
|Cellular Component:||GO:0005829 - cytosol
GO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a, GOA06]
|MultiFun Terms:||metabolism → biosynthesis of building blocks → cofactors, small molecule carriers → Coenzyme A and its modification|
|Feature Class||Location||Common Name||Citations||Comment|
|Chain||1 -> 24|
|Chain||1 -> 24||β-subunit|
|Chain||25 -> 126|
|Chain||25 -> 126||α-subunit|
|Protein-Segment||73 -> 75|
|Sequence-Conflict||120 -> 121|
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
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
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
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