ASPAT_MYCTU
ID ASPAT_MYCTU Reviewed; 435 AA.
AC O69689; F2GFU4; I6Y4D4; Q7D501;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Aspartate aminotransferase {ECO:0000303|PubMed:32327655};
DE Short=AspAT {ECO:0000303|PubMed:32327655};
DE EC=2.6.1.1 {ECO:0000269|PubMed:32327655};
GN OrderedLocusNames=Rv3722c {ECO:0000312|EMBL:CCP46548.1};
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [3] {ECO:0007744|PDB:5C6U}
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 3-430 IN COMPLEX WITH PYRIDOXAL
RP PHOSPHATE.
RG Structures of Mtb proteins conferring susceptibility to known Mtb inhibitors (MTBI);
RA Osipiuk J., Hatzos-Skintges C., Jedrzejczak R., Babnigg G., Sacchettini J.,
RA Joachimiak A.;
RT "Rv3722c aminotransferase from Mycobacterium tuberculosis.";
RL Submitted (JUN-2015) to the PDB data bank.
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) IN COMPLEXES WITH PYRIDOXAL
RP PHOSPHATE; GLUTAMIC ACID AND KYNURENINE, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=32327655; DOI=10.1038/s41467-020-15876-8;
RA Jansen R.S., Mandyoli L., Hughes R., Wakabayashi S., Pinkham J.T.,
RA Selbach B., Guinn K.M., Rubin E.J., Sacchettini J.C., Rhee K.Y.;
RT "Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen
RT metabolism in Mycobacterium tuberculosis.";
RL Nat. Commun. 11:1960-1960(2020).
CC -!- FUNCTION: Main aspartate aminotransferase that couples nitrogen
CC assimilation to aspartate synthesis. Has a weak, but significant, side
CC activity toward kynurenine (Kyn). Oxaloacetate and 2-oxoglutarate, but
CC not pyruvate, serve as amino acceptors, while Asp, Glu and Kyn serve as
CC the best amino donors. Essential for axenic growth and survival of
CC M.tuberculosis in macrophages and in mice.
CC {ECO:0000269|PubMed:32327655}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-aspartate = L-glutamate + oxaloacetate;
CC Xref=Rhea:RHEA:21824, ChEBI:CHEBI:16452, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:29991; EC=2.6.1.1;
CC Evidence={ECO:0000269|PubMed:32327655};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:32327655};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.34 mM for aspartate {ECO:0000269|PubMed:32327655};
CC KM=29.4 mM for kynurenine {ECO:0000269|PubMed:32327655};
CC Note=kcat is 136 sec(-1) with aspartate as substrate. kcat is 198
CC sec(-1) with kynurenine as substrate. {ECO:0000269|PubMed:32327655};
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene leads to virulence
CC attenuation in macrophages and mice. {ECO:0000269|PubMed:32327655}.
CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46548.1; -; Genomic_DNA.
DR RefSeq; NP_218239.2; NC_000962.3.
DR RefSeq; WP_003899653.1; NZ_NVQJ01000009.1.
DR PDB; 5C6U; X-ray; 1.83 A; A=3-430.
DR PDB; 6U78; X-ray; 2.60 A; A/B/C/D=1-435.
DR PDB; 6U7A; X-ray; 2.22 A; A/B/C/D/E/F/G/H=1-435.
DR PDBsum; 5C6U; -.
DR PDBsum; 6U78; -.
DR PDBsum; 6U7A; -.
DR AlphaFoldDB; O69689; -.
DR SMR; O69689; -.
DR IntAct; O69689; 12.
DR MINT; O69689; -.
DR STRING; 83332.Rv3722c; -.
DR PaxDb; O69689; -.
DR PRIDE; O69689; -.
DR DNASU; 885321; -.
DR GeneID; 885321; -.
DR KEGG; mtu:Rv3722c; -.
DR PATRIC; fig|83332.111.peg.4138; -.
DR TubercuList; Rv3722c; -.
DR eggNOG; COG1167; Bacteria.
DR OMA; AMDGVAT; -.
DR PhylomeDB; O69689; -.
DR BRENDA; 2.6.1.1; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0004069; F:L-aspartate:2-oxoglutarate aminotransferase activity; IEA:UniProtKB-EC.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR024551; AspAT_Ic.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF12897; Asp_aminotransf; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminotransferase; Pyridoxal phosphate; Reference proteome;
KW Transferase.
FT CHAIN 1..435
FT /note="Aspartate aminotransferase"
FT /id="PRO_0000450667"
FT BINDING 69
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:32327655, ECO:0000269|Ref.3"
FT BINDING 100..101
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:32327655, ECO:0000269|Ref.3"
FT BINDING 139..141
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:32327655"
FT BINDING 189
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:32327655, ECO:0000269|Ref.3"
FT BINDING 221
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:32327655, ECO:0000269|Ref.3"
FT BINDING 254..256
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:32327655, ECO:0000269|Ref.3"
FT BINDING 392
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:32327655"
FT HELIX 8..27
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:6U78"
FT HELIX 41..45
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 46..52
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 100..114
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 140..148
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:6U78"
FT HELIX 165..174
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 178..183
FT /evidence="ECO:0007829|PDB:5C6U"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 197..205
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:5C6U"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 236..242
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:5C6U"
FT TURN 256..258
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 272..285
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 291..301
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 304..333
FT /evidence="ECO:0007829|PDB:5C6U"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 359..367
FT /evidence="ECO:0007829|PDB:5C6U"
FT TURN 368..370
FT /evidence="ECO:0007829|PDB:5C6U"
FT TURN 376..379
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 390..393
FT /evidence="ECO:0007829|PDB:5C6U"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:5C6U"
FT HELIX 400..424
FT /evidence="ECO:0007829|PDB:5C6U"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:5C6U"
SQ SEQUENCE 435 AA; 47341 MW; B3EB892A362B5952 CRC64;
MSFDSLSPQE LAALHARHQQ DYAALQGMKL ALDLTRGKPS AEQLDLSNQL LSLPGDDYRD
PEGTDTRNYG GQHGLPGLRA IFAELLGIAV PNLIAGNNSS LELMHDIVAF SMLYGGVDSP
RPWIQEQDGI KFLCPVPGYD RHFAITETMG IEMIPIPMLQ DGPDVDLIEE LVAVDPAIKG
MWTVPVFGNP SGVTYSWETV RRLVQMRTAA PDFRLFWDNA YAVHTLTLDF PRQVDVLGLA
AKAGNPNRPY VFASTSKITF AGGGVSFFGG SLGNIAWYLQ YAGKKSIGPD KVNQLRHLRF
FGDADGVRLH MLRHQQILAP KFALVAEVLD QRLSESKIAS WTEPKGGYFI SLDVLPGTAR
RTVALAKDVG IAVTEAGASF PYRKDPDDKN IRIAPSFPSV PDLRNAVDGL ATCALLAATE
TLLNQGLASS APNVR
