NAT_MYCSM
ID NAT_MYCSM Reviewed; 275 AA.
AC O86309;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 3.
DT 25-MAY-2022, entry version 104.
DE RecName: Full=Arylamine N-acetyltransferase {ECO:0000303|PubMed:9973365};
DE Short=NAT {ECO:0000303|PubMed:9973365};
DE EC=2.3.1.5 {ECO:0000269|PubMed:12054803, ECO:0000269|PubMed:9973365};
GN Name=nat {ECO:0000303|PubMed:9973365};
OS Mycolicibacterium smegmatis (Mycobacterium smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=1772;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9973365; DOI=10.1128/jb.181.4.1343-1347.1999;
RA Payton M.A., Auty R., Delgoda R.T., Everitt M., Sim E.;
RT "Cloning and characterization of arylamine N-acetyltransferase genes from
RT Mycobacterium smegmatis and Mycobacterium tuberculosis: increased
RT expression results in isoniazid resistance.";
RL J. Bacteriol. 181:1343-1347(1999).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND ACTIVE SITE.
RX PubMed=12054803; DOI=10.1016/s0022-2836(02)00141-9;
RA Sandy J., Mushtaq A., Kawamura A., Sinclair J., Sim E., Noble M.E.M.;
RT "The structure of arylamine N-acetyltransferase from Mycobacterium
RT smegmatis -- an enzyme which inactivates the anti-tubercular drug,
RT isoniazid.";
RL J. Mol. Biol. 318:1071-1083(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF WILD-TYPE IN COMPLEX WITH
RP ISONIAZID AND OF MUTANT GLN-70, MUTAGENESIS OF CYS-70; HIS-110 AND ASP-127,
RP AND ACTIVE SITE.
RX PubMed=15869465; DOI=10.1042/bj20050277;
RA Sandy J., Mushtaq A., Holton S.J., Schartau P., Noble M.E.M., Sim E.;
RT "Investigation of the catalytic triad of arylamine N-acetyltransferases:
RT essential residues required for acetyl transfer to arylamines.";
RL Biochem. J. 390:115-123(2005).
CC -!- FUNCTION: Catalyzes the transfer of the acetyl group from acetyl
CC coenzyme A to the free amino group of arylamines and hydrazines.
CC Substrates include isoniazid, anisidine, and 4-aminoveratrole, and to a
CC much lesser extent, p-aminobenzoic acid. {ECO:0000269|PubMed:12054803,
CC ECO:0000269|PubMed:9973365}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + an arylamine = an N-acetylarylamine + CoA;
CC Xref=Rhea:RHEA:16613, ChEBI:CHEBI:13790, ChEBI:CHEBI:50471,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.5;
CC Evidence={ECO:0000269|PubMed:12054803, ECO:0000269|PubMed:9973365};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25 uM for isoniazid {ECO:0000269|PubMed:9973365};
CC KM=300 uM for anisidine {ECO:0000269|PubMed:9973365};
CC KM=650 uM for 4-aminoveratrole {ECO:0000269|PubMed:9973365};
CC KM=87 uM for isoniazid {ECO:0000269|PubMed:9973365};
CC KM=245 uM for 4-anisidine {ECO:0000269|PubMed:9973365};
CC KM=1.42 mM for 4-aminoveratrole {ECO:0000269|PubMed:9973365};
CC Vmax=63 nmol/min/mg enzyme with isoniazid as substrate
CC {ECO:0000269|PubMed:9973365};
CC Vmax=4.8 nmol/min/mg enzyme with anisidine as substrate
CC {ECO:0000269|PubMed:9973365};
CC Vmax=16.2 nmol/min/mg enzyme with 4-aminoveratrole as substrate
CC {ECO:0000269|PubMed:9973365};
CC Vmax=115 nmol/min/mg enzyme with isoniazid as substrate
CC {ECO:0000269|PubMed:9973365};
CC Vmax=114 nmol/min/mg enzyme with 4-anisidine as substrate
CC {ECO:0000269|PubMed:9973365};
CC Vmax=6.5 umol/min/mg enzyme with 4-aminoveratrole as substrate
CC {ECO:0000269|PubMed:9973365};
CC -!- SUBUNIT: Homodimer and homotetramer. {ECO:0000269|PubMed:12054803}.
CC -!- SIMILARITY: Belongs to the arylamine N-acetyltransferase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA07100.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ006588; CAA07100.2; ALT_INIT; Genomic_DNA.
DR PDB; 1GX3; X-ray; 1.70 A; A/B/C/D=1-275.
DR PDB; 1W5R; X-ray; 1.45 A; A/B=1-275.
DR PDB; 1W6F; X-ray; 2.10 A; A/B/C/D=1-275.
DR PDBsum; 1GX3; -.
DR PDBsum; 1W5R; -.
DR PDBsum; 1W6F; -.
DR AlphaFoldDB; O86309; -.
DR SMR; O86309; -.
DR BindingDB; O86309; -.
DR ChEMBL; CHEMBL6060; -.
DR BRENDA; 2.3.1.5; 3512.
DR SABIO-RK; O86309; -.
DR EvolutionaryTrace; O86309; -.
DR GO; GO:0004060; F:arylamine N-acetyltransferase activity; IEA:UniProtKB-EC.
DR InterPro; IPR001447; Arylamine_N-AcTrfase.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR PANTHER; PTHR11786; PTHR11786; 1.
DR Pfam; PF00797; Acetyltransf_2; 1.
DR PRINTS; PR01543; ANATRNSFRASE.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Transferase.
FT CHAIN 1..275
FT /note="Arylamine N-acetyltransferase"
FT /id="PRO_0000107918"
FT ACT_SITE 70
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000305|PubMed:12054803,
FT ECO:0000305|PubMed:15869465"
FT ACT_SITE 110
FT /evidence="ECO:0000305|PubMed:12054803,
FT ECO:0000305|PubMed:15869465"
FT ACT_SITE 127
FT /evidence="ECO:0000305|PubMed:12054803,
FT ECO:0000305|PubMed:15869465"
FT MUTAGEN 70
FT /note="C->A,S,Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15869465"
FT MUTAGEN 110
FT /note="H->A,R,W: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15869465"
FT MUTAGEN 127
FT /note="D->A,N,W: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15869465"
FT HELIX 5..11
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 22..35
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 54..61
FT /evidence="ECO:0007829|PDB:1W5R"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 70..84
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 87..95
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 108..116
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:1GX3"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 162..169
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 186..198
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 203..206
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 215..222
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 225..230
FT /evidence="ECO:0007829|PDB:1W5R"
FT STRAND 233..241
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:1W5R"
FT HELIX 265..271
FT /evidence="ECO:0007829|PDB:1W5R"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:1W5R"
SQ SEQUENCE 275 AA; 30174 MW; C35800574905D3B9 CRC64;
MAMDLGGYLT RIGLDGRPRP DLGTLHAIVA AHNRSIPFEN LDPLLGIPVA DLSAEALFAK
LVDRRRGGYC YEHNGLLGYV LEELGFEVER LSGRVVWMRA DDAPLPAQTH NVLSVAVPGA
DGRYLVDVGF GGQTLTSPIR LEAGPVQQTR HEPYRLTRHG DDHTLAAQVR GEWQPLYTFT
TEPRPRIDLE VGSWYVSTHP GSHFVTGLTV AVVTDDARYN LRGRNLAVHR SGATEHIRFD
SAAQVLDAIV NRFGIDLGDL AGRDVQARVA EVLDT
