ALR_MYCTU
ID ALR_MYCTU Reviewed; 386 AA.
AC P9WQA9; L0TFK3; P0A4X2; Q50705;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Alanine racemase {ECO:0000255|HAMAP-Rule:MF_01201};
DE EC=5.1.1.1 {ECO:0000255|HAMAP-Rule:MF_01201};
GN Name=alr; OrderedLocusNames=Rv3423c; ORFNames=MTCY78.06;
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 [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11267762; DOI=10.1111/j.1574-6968.2001.tb10547.x;
RA Strych U., Penland R.L., Jimenez M., Krause K.L., Benedik M.J.;
RT "Characterization of the alanine racemases from two Mycobacteria.";
RL FEMS Microbiol. Lett. 196:93-98(2001).
RN [2]
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 [3]
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 [4]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE,
RP SUBUNIT, COFACTOR, AND PYRIDOXAL PHOSPHATE AT LYS-44.
RX PubMed=15683232; DOI=10.1021/bi0486583;
RA LeMagueres P., Im H., Ebalunode J., Strych U., Benedik M.J., Briggs J.M.,
RA Kohn H., Krause K.L.;
RT "The 1.9 A crystal structure of alanine racemase from Mycobacterium
RT tuberculosis contains a conserved entryway into the active site.";
RL Biochemistry 44:1471-1481(2005).
CC -!- FUNCTION: Catalyzes the interconversion of L-alanine and D-alanine. D-
CC alanine plays a key role in peptidoglycan cross-linking.
CC {ECO:0000269|PubMed:11267762}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-alanine = D-alanine; Xref=Rhea:RHEA:20249,
CC ChEBI:CHEBI:57416, ChEBI:CHEBI:57972; EC=5.1.1.1;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01201,
CC ECO:0000269|PubMed:11267762};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01201,
CC ECO:0000269|PubMed:15683232};
CC -!- ACTIVITY REGULATION: Inhibited by the antituberculous drug D-
CC cycloserine (DCS), which is a structural analog of D-alanine.
CC {ECO:0000269|PubMed:11267762}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.1 mM for D-alanine {ECO:0000269|PubMed:11267762};
CC KM=1.2 mM for L-alanine {ECO:0000269|PubMed:11267762};
CC Vmax=0.46 umol/min/mg enzyme toward D-alanine
CC {ECO:0000269|PubMed:11267762};
CC Vmax=0.51 umol/min/mg enzyme toward L-alanine
CC {ECO:0000269|PubMed:11267762};
CC -!- PATHWAY: Amino-acid biosynthesis; D-alanine biosynthesis; D-alanine
CC from L-alanine: step 1/1. {ECO:0000255|HAMAP-Rule:MF_01201}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15683232}.
CC -!- SIMILARITY: Belongs to the alanine racemase family. {ECO:0000255|HAMAP-
CC Rule:MF_01201}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD51033.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CCP46245.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF172731; AAD51033.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL123456; CCP46245.1; ALT_INIT; Genomic_DNA.
DR PIR; D70738; D70738.
DR RefSeq; NP_217940.1; NC_000962.3.
DR RefSeq; WP_023637501.1; NC_018143.2.
DR PDB; 1XFC; X-ray; 1.90 A; A/B=3-386.
DR PDB; 6SCZ; X-ray; 1.57 A; A/B=3-386.
DR PDBsum; 1XFC; -.
DR PDBsum; 6SCZ; -.
DR AlphaFoldDB; P9WQA9; -.
DR SMR; P9WQA9; -.
DR STRING; 83332.Rv3423c; -.
DR ChEMBL; CHEMBL2031; -.
DR DrugCentral; P9WQA9; -.
DR PaxDb; P9WQA9; -.
DR DNASU; 887634; -.
DR GeneID; 887634; -.
DR KEGG; mtu:Rv3423c; -.
DR PATRIC; fig|83332.12.peg.3820; -.
DR TubercuList; Rv3423c; -.
DR eggNOG; COG0787; Bacteria.
DR OMA; WEILCGF; -.
DR BRENDA; 5.1.1.1; 3445.
DR SABIO-RK; P9WQA9; -.
DR UniPathway; UPA00042; UER00497.
DR PRO; PR:P9WQA9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0008784; F:alanine racemase activity; IDA:MTBBASE.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:MTBBASE.
DR GO; GO:0030632; P:D-alanine biosynthetic process; IDA:MTBBASE.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IDA:MTBBASE.
DR Gene3D; 2.40.37.10; -; 1.
DR Gene3D; 3.20.20.10; -; 1.
DR HAMAP; MF_01201; Ala_racemase; 1.
DR InterPro; IPR000821; Ala_racemase.
DR InterPro; IPR009006; Ala_racemase/Decarboxylase_C.
DR InterPro; IPR011079; Ala_racemase_C.
DR InterPro; IPR001608; Ala_racemase_N.
DR InterPro; IPR020622; Ala_racemase_pyridoxalP-BS.
DR InterPro; IPR029066; PLP-binding_barrel.
DR Pfam; PF00842; Ala_racemase_C; 1.
DR Pfam; PF01168; Ala_racemase_N; 1.
DR PRINTS; PR00992; ALARACEMASE.
DR SMART; SM01005; Ala_racemase_C; 1.
DR SUPFAM; SSF50621; SSF50621; 1.
DR SUPFAM; SSF51419; SSF51419; 1.
DR TIGRFAMs; TIGR00492; alr; 1.
DR PROSITE; PS00395; ALANINE_RACEMASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase; Pyridoxal phosphate; Reference proteome.
FT CHAIN 1..386
FT /note="Alanine racemase"
FT /id="PRO_0000114539"
FT ACT_SITE 44
FT /note="Proton acceptor; specific for D-alanine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01201"
FT ACT_SITE 273
FT /note="Proton acceptor; specific for L-alanine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01201"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01201"
FT BINDING 321
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01201"
FT MOD_RES 44
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:15683232"
FT STRAND 13..19
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 20..34
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 44..48
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 52..61
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 72..80
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 99..103
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 113..126
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 130..136
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:6SCZ"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 150..162
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 165..172
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 184..202
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 215..220
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:6SCZ"
FT TURN 233..237
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:6SCZ"
FT TURN 245..248
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:6SCZ"
FT TURN 301..303
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 305..308
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 311..317
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 324..332
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 354..361
FT /evidence="ECO:0007829|PDB:6SCZ"
FT HELIX 365..369
FT /evidence="ECO:0007829|PDB:6SCZ"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:6SCZ"
SQ SEQUENCE 386 AA; 40926 MW; 806225696ACB0BFE CRC64;
MAMTPISQTP GLLAEAMVDL GAIEHNVRVL REHAGHAQLM AVVKADGYGH GATRVAQTAL
GAGAAELGVA TVDEALALRA DGITAPVLAW LHPPGIDFGP ALLADVQVAV SSLRQLDELL
HAVRRTGRTA TVTVKVDTGL NRNGVGPAQF PAMLTALRQA MAEDAVRLRG LMSHMVYADK
PDDSINDVQA QRFTAFLAQA REQGVRFEVA HLSNSSATMA RPDLTFDLVR PGIAVYGLSP
VPALGDMGLV PAMTVKCAVA LVKSIRAGEG VSYGHTWIAP RDTNLALLPI GYADGVFRSL
GGRLEVLING RRCPGVGRIC MDQFMVDLGP GPLDVAEGDE AILFGPGIRG EPTAQDWADL
VGTIHYEVVT SPRGRITRTY REAENR
