ID   PAND_MYCTA              Reviewed;         139 AA.
AC   A5U8S6;
DT   02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   10-JUL-2007, sequence version 1.
DT   03-AUG-2022, entry version 80.
DE   RecName: Full=Aspartate 1-decarboxylase {ECO:0000255|HAMAP-Rule:MF_00446};
DE            EC=4.1.1.11 {ECO:0000255|HAMAP-Rule:MF_00446};
DE   AltName: Full=Aspartate alpha-decarboxylase {ECO:0000255|HAMAP-Rule:MF_00446};
DE   Contains:
DE     RecName: Full=Aspartate 1-decarboxylase beta chain {ECO:0000255|HAMAP-Rule:MF_00446};
DE   Contains:
DE     RecName: Full=Aspartate 1-decarboxylase alpha chain {ECO:0000255|HAMAP-Rule:MF_00446};
DE   Flags: Precursor;
GN   Name=panD {ECO:0000255|HAMAP-Rule:MF_00446}; OrderedLocusNames=MRA_3640;
OS   Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=419947;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25177 / H37Ra;
RX   PubMed=18584054; DOI=10.1371/journal.pone.0002375;
RA   Zheng H., Lu L., Wang B., Pu S., Zhang X., Zhu G., Shi W., Zhang L.,
RA   Wang H., Wang S., Zhao G., Zhang Y.;
RT   "Genetic basis of virulence attenuation revealed by comparative genomic
RT   analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv.";
RL   PLoS ONE 3:E2375-E2375(2008).
RN   [2]
RP   FUNCTION, ACTIVITY REGULATION, POSSIBLE ANTIBIOTIC RESISTANCE, AND
RP   MUTAGENESIS OF MET-117; 127-ASN--GLY-139; LEU-136 AND VAL-138.
RC   STRAIN=ATCC 25177 / H37Ra;
RX   PubMed=26038753; DOI=10.1038/emi.2014.61;
RA   Shi W., Chen J., Feng J., Cui P., Zhang S., Weng X., Zhang W., Zhang Y.;
RT   "Aspartate decarboxylase (PanD) as a new target of pyrazinamide in
RT   Mycobacterium tuberculosis.";
RL   Emerg. Microbes Infect. 3:E58-E58(2014).
CC   -!- FUNCTION: Catalyzes the pyruvoyl-dependent decarboxylation of aspartate
CC       to produce beta-alanine. {ECO:0000255|HAMAP-Rule:MF_00446}.
CC   -!- FUNCTION: Overexpression of wild-type or mutant proteins confers
CC       resistance to pyrazinoic acid (POA), the active form of the anti-
CC       tuberculosis prodrug pyrazinamide (PZA), when grown on agar plates.
CC       {ECO:0000269|PubMed:26038753}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+) + L-aspartate = beta-alanine + CO2; Xref=Rhea:RHEA:19497,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:29991,
CC         ChEBI:CHEBI:57966; EC=4.1.1.11; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_00446};
CC   -!- COFACTOR:
CC       Name=pyruvate; Xref=ChEBI:CHEBI:15361;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_00446};
CC       Note=Binds 1 pyruvoyl group covalently per subunit. {ECO:0000255|HAMAP-
CC       Rule:MF_00446};
CC   -!- ACTIVITY REGULATION: Partially inhibited by POA but not by PZA or
CC       nicotinamide, probably also inhibited by calcium pantothenate.
CC       {ECO:0000269|PubMed:26038753}.
CC   -!- PATHWAY: Cofactor biosynthesis; (R)-pantothenate biosynthesis; beta-
CC       alanine from L-aspartate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00446}.
CC   -!- SUBUNIT: Heterooctamer of four alpha and four beta subunits.
CC       {ECO:0000255|HAMAP-Rule:MF_00446}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00446}.
CC   -!- PTM: Is synthesized initially as an inactive proenzyme, which is
CC       activated by self-cleavage at a specific serine bond to produce a beta-
CC       subunit with a hydroxyl group at its C-terminus and an alpha-subunit
CC       with a pyruvoyl group at its N-terminus. {ECO:0000255|HAMAP-
CC       Rule:MF_00446}.
CC   -!- MISCELLANEOUS: 30 POA or PZA-resistant mutants were identified in this
CC       gene by selection at pH 5.7 - 6.8. The antituberculosis activity of POA
CC       is antagonized by beta-alanine and pantothenate, the immediate and
CC       final reaction products of this enzyme (PubMed:26038753). Experiments
CC       in strain H37Rv suggest however that the PZA target may not be PanD (By
CC       similarity). {ECO:0000250|UniProtKB:P9WIL3,
CC       ECO:0000269|PubMed:26038753}.
CC   -!- SIMILARITY: Belongs to the PanD family. {ECO:0000255|HAMAP-
CC       Rule:MF_00446}.
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DR   EMBL; CP000611; ABQ75426.1; -; Genomic_DNA.
DR   RefSeq; WP_003419523.1; NZ_CP016972.1.
DR   AlphaFoldDB; A5U8S6; -.
DR   SMR; A5U8S6; -.
DR   STRING; 419947.MRA_3640; -.
DR   EnsemblBacteria; ABQ75426; ABQ75426; MRA_3640.
DR   KEGG; mra:MRA_3640; -.
DR   eggNOG; COG0853; Bacteria.
DR   HOGENOM; CLU_115305_2_0_11; -.
DR   OMA; MLYSKIH; -.
DR   OrthoDB; 1751990at2; -.
DR   UniPathway; UPA00028; UER00002.
DR   Proteomes; UP000001988; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004068; F:aspartate 1-decarboxylase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0006523; P:alanine biosynthetic process; IEA:InterPro.
DR   GO; GO:0015940; P:pantothenate biosynthetic process; IEA:UniProtKB-UniRule.
DR   GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR   CDD; cd06919; Asp_decarbox; 1.
DR   HAMAP; MF_00446; PanD; 1.
DR   InterPro; IPR009010; Asp_de-COase-like_dom_sf.
DR   InterPro; IPR003190; Asp_decarbox.
DR   PANTHER; PTHR21012; PTHR21012; 1.
DR   Pfam; PF02261; Asp_decarbox; 1.
DR   PIRSF; PIRSF006246; Asp_decarbox; 1.
DR   SUPFAM; SSF50692; SSF50692; 1.
DR   TIGRFAMs; TIGR00223; panD; 1.
PE   1: Evidence at protein level;
KW   Antibiotic resistance; Autocatalytic cleavage; Cytoplasm; Decarboxylase;
KW   Lyase; Pantothenate biosynthesis; Pyruvate; Schiff base; Zymogen.
FT   CHAIN           1..24
FT                   /note="Aspartate 1-decarboxylase beta chain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00446"
FT                   /id="PRO_0000307029"
FT   CHAIN           25..139
FT                   /note="Aspartate 1-decarboxylase alpha chain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00446"
FT                   /id="PRO_0000307030"
FT   ACT_SITE        25
FT                   /note="Schiff-base intermediate with substrate; via pyruvic
FT                   acid"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00446"
FT   ACT_SITE        58
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00446"
FT   BINDING         57
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00446"
FT   BINDING         73..75
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00446"
FT   MOD_RES         25
FT                   /note="Pyruvic acid (Ser)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00446"
FT   MUTAGEN         117
FT                   /note="M->I: Confers POA resistance, partially inhibited by
FT                   POA; identified in 24/30 mutants."
FT                   /evidence="ECO:0000269|PubMed:26038753"
FT   MUTAGEN         127..139
FT                   /note="Missing: Confers POA resistance."
FT                   /evidence="ECO:0000269|PubMed:26038753"
FT   MUTAGEN         136
FT                   /note="L->R: Confers POA resistance."
FT                   /evidence="ECO:0000269|PubMed:26038753"
FT   MUTAGEN         138
FT                   /note="V->A,E,G: Confers POA resistance."
FT                   /evidence="ECO:0000269|PubMed:26038753"
SQ   SEQUENCE   139 AA;  14885 MW;  C5BFDC1C996ED9C6 CRC64;
     MLRTMLKSKI HRATVTCADL HYVGSVTIDA DLMDAADLLE GEQVTIVDID NGARLVTYAI
     TGERGSGVIG INGAAAHLVH PGDLVILIAY ATMDDARART YQPRIVFVDA YNKPIDMGHD
     PAFVPENAGE LLDPRLGVG