PAND_MYCTU
ID PAND_MYCTU Reviewed; 139 AA.
AC P9WIL3; L0TDA1; O06281; P65660;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Aspartate 1-decarboxylase {ECO:0000255|HAMAP-Rule:MF_00446};
DE EC=4.1.1.11 {ECO:0000255|HAMAP-Rule:MF_00446, ECO:0000269|PubMed:12182836};
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=Rv3601c;
GN ORFNames=MTCY07H7B.21;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP PROTEIN SEQUENCE OF 26-34, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND AUTOCLEAVAGE.
RC STRAIN=H37Rv;
RX PubMed=12182836; DOI=10.1016/s1046-5928(02)00039-6;
RA Chopra S., Pai H., Ranganathan A.;
RT "Expression, purification, and biochemical characterization of
RT Mycobacterium tuberculosis aspartate decarboxylase, PanD.";
RL Protein Expr. Purif. 25:533-540(2002).
RN [3]
RP DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RC STRAIN=H37Rv;
RX PubMed=12219086; DOI=10.1038/nm765;
RA Sambandamurthy V.K., Wang X., Chen B., Russell R.G., Derrick S.,
RA Collins F.M., Morris S.L., Jacobs W.R. Jr.;
RT "A pantothenate auxotroph of Mycobacterium tuberculosis is highly
RT attenuated and protects mice against tuberculosis.";
RL Nat. Med. 8:1171-1174(2002).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP FUNCTION, POSSIBLE ANTIBIOTIC RESISTANCE, AND MUTAGENESIS OF HIS-21;
RP ILE-49; ALA-128; GLU-130 AND VAL-138.
RC STRAIN=H37Rv;
RX PubMed=26038471; DOI=10.1038/emi.2013.38;
RA Zhang S., Chen J., Shi W., Liu W., Zhang W., Zhang Y.;
RT "Mutations in panD encoding aspartate decarboxylase are associated with
RT pyrazinamide resistance in Mycobacterium tuberculosis.";
RL Emerg. Microbes Infect. 2:E34-E34(2013).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=25246400; DOI=10.1128/aac.04028-14;
RA Dillon N.A., Peterson N.D., Rosen B.C., Baughn A.D.;
RT "Pantothenate and pantetheine antagonize the antitubercular activity of
RT pyrazinamide.";
RL Antimicrob. Agents Chemother. 58:7258-7263(2014).
RN [7]
RP POSSIBLE ANTIBIOTIC RESISTANCE.
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).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS).
RC STRAIN=H37Rv;
RX PubMed=17001646; DOI=10.1002/prot.21126;
RA Gopalan G., Chopra S., Ranganathan A., Swaminathan K.;
RT "Crystal structure of uncleaved L-aspartate-alpha-decarboxylase from
RT Mycobacterium tuberculosis.";
RL Proteins 65:796-802(2006).
CC -!- FUNCTION: Catalyzes the pyruvoyl-dependent decarboxylation of aspartate
CC to produce beta-alanine. {ECO:0000255|HAMAP-Rule:MF_00446,
CC ECO:0000305|PubMed:12182836}.
CC -!- FUNCTION: Overexpression of wild-type protein confers resistance to
CC pyrazinoic acid (POA), the active form of the anti-tuberculosis prodrug
CC pyrazinamide (PZA). {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, ECO:0000269|PubMed:12182836};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=219.6 uM for L-aspartate {ECO:0000269|PubMed:12182836};
CC Note=kcat is 0.65 sec(-1), specific activity 2100 nmol/min/mg for L-
CC aspartate. {ECO:0000269|PubMed:12182836};
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, ECO:0000305|PubMed:12182836}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00446,
CC ECO:0000305|PubMed:12182836}.
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. Cleavage is not necessary for
CC tetramerization upon expression in E.coli; protein expressed in E.coli
CC is fully process in vitro after 48 hours at 37 degrees Celsius
CC (PubMed:12182836). {ECO:0000255|HAMAP-Rule:MF_00446,
CC ECO:0000305|PubMed:12182836}.
CC -!- DISRUPTION PHENOTYPE: Simultaneous disruption of panD and panC gives a
CC mutant unable to grow in the absence of panothenate. The double mutant
CC has a highly attenuated disease response in BALB/c and SCID mice;
CC immunocompromised BALB/c SCID mice survive on average 36 weeks as
CC opposed to 5 weeks for mice infected with wild-type bacteria, while
CC immunocompetent BALB/c mice survive indefinitely. In wild-type mice
CC bacteria grow for 3 weeks then undergo a steady decline, bacteria
CC persist over 8 months in SCID mice (PubMed:12219086). The double mutant
CC is sensitive to PZA but not POA in liquid culture, beta-alanine but not
CC pantothenate antagonize the effect of PZA at pH 5.8 (PubMed:25246400).
CC {ECO:0000269|PubMed:12219086, ECO:0000269|PubMed:25246400}.
CC -!- BIOTECHNOLOGY: Subcutaneous immunization with the double panD and panC
CC bacterial disruption mutant protects mice for over a year against
CC subsequent virulent M.tuberculosis (strain Erdman) infections; mice
CC show mild lung inflammation and fibrosis despite a chronic bacterila
CC infection. This is a promising attenuated vaccine strain.
CC {ECO:0000269|PubMed:12219086}.
CC -!- MISCELLANEOUS: Pantothenate, pantetheine and beta-alanine containing
CC compounds (all part of the panthothenate/coenzyme A biosynthetic
CC pathway) antagonize PZA and POA antitubercular activity. However
CC cultivation of the double panD and panC mutant with low levels of
CC pantetheine (an intermediate between pantothenate and coenzyme A, at pH
CC 5.8) restores sensitivity to PZA, suggesting PanD is not the PZA
CC target. {ECO:0000269|PubMed:25246400}.
CC -!- SIMILARITY: Belongs to the PanD family. {ECO:0000255|HAMAP-
CC Rule:MF_00446}.
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DR EMBL; AL123456; CCP46424.1; -; Genomic_DNA.
DR PIR; B70955; B70955.
DR RefSeq; NP_218118.1; NC_000962.3.
DR RefSeq; WP_003419523.1; NZ_NVQJ01000056.1.
DR PDB; 2C45; X-ray; 2.99 A; A/B/C/D/E/F/G/H=1-139.
DR PDBsum; 2C45; -.
DR AlphaFoldDB; P9WIL3; -.
DR SMR; P9WIL3; -.
DR STRING; 83332.Rv3601c; -.
DR PaxDb; P9WIL3; -.
DR DNASU; 885596; -.
DR GeneID; 885596; -.
DR KEGG; mtu:Rv3601c; -.
DR TubercuList; Rv3601c; -.
DR eggNOG; COG0853; Bacteria.
DR OMA; MLYSKIH; -.
DR PhylomeDB; P9WIL3; -.
DR UniPathway; UPA00028; UER00002.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR GO; GO:0004068; F:aspartate 1-decarboxylase activity; IDA:MTBBASE.
DR GO; GO:0006523; P:alanine biosynthetic process; IDA:MTBBASE.
DR GO; GO:0015940; P:pantothenate biosynthetic process; IDA:MTBBASE.
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 3D-structure; Autocatalytic cleavage; Cytoplasm; Decarboxylase;
KW Direct protein sequencing; Lyase; Pantothenate biosynthesis; Pyruvate;
KW Reference proteome; Schiff base; Virulence; Zymogen.
FT CHAIN 1..24
FT /note="Aspartate 1-decarboxylase beta chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00446,
FT ECO:0000305|PubMed:12182836"
FT /id="PRO_0000023121"
FT CHAIN 25..139
FT /note="Aspartate 1-decarboxylase alpha chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00446,
FT ECO:0000305|PubMed:12182836"
FT /id="PRO_0000023122"
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 21
FT /note="H->R: In S11; may confer PZA resistance; when
FT associated with V-49."
FT /evidence="ECO:0000269|PubMed:26038471"
FT MUTAGEN 49
FT /note="I->V: In S11; may confer PZA resistance; when
FT associated with R-21."
FT /evidence="ECO:0000269|PubMed:26038471"
FT MUTAGEN 128
FT /note="A->S: In S6; may confer PZA resistance."
FT /evidence="ECO:0000269|PubMed:26038471"
FT MUTAGEN 130
FT /note="E->G: In S13; may confer PZA resistance."
FT /evidence="ECO:0000269|PubMed:26038471"
FT MUTAGEN 138
FT /note="V->A: In S9, S10; may confer PZA resistance."
FT /evidence="ECO:0000269|PubMed:26038471"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 18..22
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:2C45"
FT HELIX 30..35
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:2C45"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:2C45"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 69..74
FT /evidence="ECO:0007829|PDB:2C45"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:2C45"
FT HELIX 95..99
FT /evidence="ECO:0007829|PDB:2C45"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:2C45"
SQ SEQUENCE 139 AA; 14885 MW; C5BFDC1C996ED9C6 CRC64;
MLRTMLKSKI HRATVTCADL HYVGSVTIDA DLMDAADLLE GEQVTIVDID NGARLVTYAI
TGERGSGVIG INGAAAHLVH PGDLVILIAY ATMDDARART YQPRIVFVDA YNKPIDMGHD
PAFVPENAGE LLDPRLGVG
