S3AD_SALTY
ID S3AD_SALTY Reviewed; 262 AA.
AC Q8ZPX9;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Aminoglycoside (3'') (9) adenylyltransferase {ECO:0000303|PubMed:26527143};
DE EC=2.7.7.47 {ECO:0000305|PubMed:29871922};
DE AltName: Full=AadA {ECO:0000303|PubMed:26527143};
DE AltName: Full=Aminoglycoside nucleotidyltransferase (3'') (9) adenyltransferase {ECO:0000303|PubMed:26527143};
DE Short=ANT(3'') (9) adenyltransferase {ECO:0000303|PubMed:26527143};
GN Name=aadA; OrderedLocusNames=STM1264;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [2]
RP FUNCTION IN SPECTINOMYCIN AND STREPTOMYCIN RESISTANCE, AND INDUCTION IN
RP MINIMAL MEDIA.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=21507083; DOI=10.1111/j.1365-2958.2011.07657.x;
RA Koskiniemi S., Praenting M., Gullberg E., Naesvall J., Andersson D.I.;
RT "Activation of cryptic aminoglycoside resistance in Salmonella enterica.";
RL Mol. Microbiol. 80:1464-1478(2011).
RN [3] {ECO:0007744|PDB:4CS6}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS), FUNCTION IN SPECTINOMYCIN AND
RP STREPTOMYCIN RESISTANCE, ACTIVE SITE, SUBUNIT, DOMAIN, DISRUPTION
RP PHENOTYPE, MUTAGENESIS OF GLU-87; TRP-112; ASP-182; ARG-192 AND LYS-205,
RP AND ATP-BINDING.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=26527143; DOI=10.1107/s1399004715016429;
RA Chen Y., Nasvall J., Wu S., Andersson D.I., Selmer M.;
RT "Structure of AadA from Salmonella enterica: a monomeric aminoglycoside
RT (3'')(9) adenyltransferase.";
RL Acta Crystallogr. D 71:2267-2277(2015).
RN [4] {ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA, ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN COMPLEX WITH MG-ATP WITH AND
RP WITHOUT ANTIBIOTICS, FUNCTION IN SPECTINOMYCIN AND STREPTOMYCIN RESISTANCE,
RP CATALYTIC ACTIVITY, ACTIVE SITE, DOMAIN, MUTAGENESIS OF GLU-87; TRP-173 AND
RP ASP-178, AND ATP-BINDING.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=29871922; DOI=10.1074/jbc.ra118.003989;
RA Stern A.L., Van der Verren S.E., Kanchugal P S., Nasvall J.,
RA Gutierrez de Teran H., Selmer M.;
RT "Structural mechanism of AadA, a dual-specificity aminoglycoside
RT adenylyltransferase from Salmonella enterica.";
RL J. Biol. Chem. 293:11481-11490(2018).
CC -!- FUNCTION: Mediates bacterial resistance to the antibiotics streptomycin
CC and spectinomycin, does not confer resistance to kanamycin
CC (PubMed:26527143). Binds ATP first, then antibiotic (PubMed:26527143,
CC PubMed:29871922). {ECO:0000269|PubMed:26527143,
CC ECO:0000269|PubMed:29871922}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + streptomycin = 3''-O-adenylylstreptomycin + diphosphate;
CC Xref=Rhea:RHEA:20245, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58007, ChEBI:CHEBI:58605; EC=2.7.7.47;
CC Evidence={ECO:0000305|PubMed:29871922};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + spectinomycin = 9-O-adenylylspectinomycin + diphosphate;
CC Xref=Rhea:RHEA:63228, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:146260, ChEBI:CHEBI:146261;
CC Evidence={ECO:0000305|PubMed:29871922};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:26527143}.
CC -!- INDUCTION: Induced by growth in minimal media (at protein level). Under
CC positive control of the stringent response regulator guanosine 3',5'-
CC bis(diphosphate) (ppGpp). {ECO:0000269|PubMed:21507083}.
CC -!- DOMAIN: Has an N-terminal adenylyltranferase and a C-terminal helical
CC domain, with an ATP-binding cleft between them (PubMed:26527143,
CC PubMed:29871922). Upon ATP binding the two domains reposition,
CC antibiotics bind in this cleft (PubMed:29871922).
CC {ECO:0000269|PubMed:26527143, ECO:0000269|PubMed:29871922}.
CC -!- DISRUPTION PHENOTYPE: Loss of streptomycin and spectinomycin
CC resistance. {ECO:0000269|PubMed:26527143}.
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DR EMBL; AE006468; AAL20189.1; -; Genomic_DNA.
DR RefSeq; NP_460230.1; NC_003197.2.
DR RefSeq; WP_000175803.1; NC_003197.2.
DR PDB; 4CS6; X-ray; 2.50 A; A=1-262.
DR PDB; 5G4A; X-ray; 1.90 A; A/B=1-262.
DR PDB; 5LPA; X-ray; 1.40 A; A/B=1-262.
DR PDB; 5LUH; X-ray; 1.73 A; A/B=1-262.
DR PDB; 6FZB; X-ray; 2.05 A; A/B=1-262.
DR PDBsum; 4CS6; -.
DR PDBsum; 5G4A; -.
DR PDBsum; 5LPA; -.
DR PDBsum; 5LUH; -.
DR PDBsum; 6FZB; -.
DR AlphaFoldDB; Q8ZPX9; -.
DR SMR; Q8ZPX9; -.
DR STRING; 99287.STM1264; -.
DR PaxDb; Q8ZPX9; -.
DR EnsemblBacteria; AAL20189; AAL20189; STM1264.
DR GeneID; 1252782; -.
DR KEGG; stm:STM1264; -.
DR PATRIC; fig|99287.12.peg.1341; -.
DR HOGENOM; CLU_071584_0_0_6; -.
DR OMA; QQDWDIV; -.
DR PhylomeDB; Q8ZPX9; -.
DR BioCyc; SENT99287:STM1264-MON; -.
DR BRENDA; 2.7.7.47; 5542.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0070566; F:adenylyltransferase activity; IEA:InterPro.
DR GO; GO:0009012; F:aminoglycoside 3''-adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IMP:UniProtKB.
DR Gene3D; 3.30.460.10; -; 1.
DR InterPro; IPR024172; AadA/Aad9.
DR InterPro; IPR025184; DUF4111.
DR InterPro; IPR043519; NT_sf.
DR InterPro; IPR002934; Polymerase_NTP_transf_dom.
DR Pfam; PF13427; DUF4111; 1.
DR Pfam; PF01909; NTP_transf_2; 1.
DR PIRSF; PIRSF000819; Streptomycin_3-adenylyltransf; 1.
DR SUPFAM; SSF81301; SSF81301; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; ATP-binding; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW Transferase.
FT CHAIN 1..262
FT /note="Aminoglycoside (3'') (9) adenylyltransferase"
FT /id="PRO_0000450270"
FT REGION 1..157
FT /note="Adenylyltransferase domain"
FT /evidence="ECO:0000269|PubMed:26527143"
FT REGION 158..262
FT /note="Helical domain"
FT /evidence="ECO:0000269|PubMed:26527143"
FT ACT_SITE 87
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:26527143,
FT ECO:0000305|PubMed:29871922"
FT BINDING 36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 46
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 47
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 47
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 47
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 49
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 49
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 173..178
FT /ligand="streptomycin"
FT /ligand_id="ChEBI:CHEBI:58007"
FT /ligand_note="substrate"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5LPA, ECO:0007744|PDB:5LUH,
FT ECO:0007744|PDB:6FZB"
FT BINDING 185
FT /ligand="streptomycin"
FT /ligand_id="ChEBI:CHEBI:58007"
FT /ligand_note="substrate"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5LPA, ECO:0007744|PDB:5LUH"
FT BINDING 205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT BINDING 231
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29871922,
FT ECO:0007744|PDB:5G4A, ECO:0007744|PDB:5LPA,
FT ECO:0007744|PDB:5LUH, ECO:0007744|PDB:6FZB"
FT MUTAGEN 87
FT /note="E->A,Q: Loss of streptomycin and spectinomycin
FT resistance, 4-fold decreased ATP-binding, significantly
FT decreased streptomycin binding, no spectinomycin binding."
FT /evidence="ECO:0000269|PubMed:26527143,
FT ECO:0000269|PubMed:29871922"
FT MUTAGEN 112
FT /note="W->A: 8-fold reduced MIC for streptomycin, loss of
FT spectinomycin resistance."
FT /evidence="ECO:0000269|PubMed:26527143"
FT MUTAGEN 112
FT /note="W->F: 2.7-fold reduced MIC for streptomycin, loss of
FT spectinomycin resistance, no change in ATP or antibiotic
FT binding."
FT /evidence="ECO:0000269|PubMed:26527143"
FT MUTAGEN 173
FT /note="W->A: 10-fold reduced MIC for streptomycin, no
FT change in spectinomycin resistance, reduced streptomycin
FT but not spectinomycin binding."
FT /evidence="ECO:0000269|PubMed:29871922"
FT MUTAGEN 178
FT /note="D->A: 5-fold reduced MIC for streptomycin, 1.5-fold
FT reduced MIC for spectinomycin resistance, reduced
FT streptomycin but not spectinomycin binding."
FT /evidence="ECO:0000269|PubMed:29871922"
FT MUTAGEN 182
FT /note="D->A,N: 4-5-fold reduced MIC for streptomycin and
FT spectinomycin, very little spectinomycin binding."
FT /evidence="ECO:0000269|PubMed:26527143"
FT MUTAGEN 192
FT /note="R->A: Loss of streptomycin and spectinomycin
FT resistance, no ATP-binding, very little antibiotic
FT binding."
FT /evidence="ECO:0000269|PubMed:26527143"
FT MUTAGEN 205
FT /note="K->A: Loss of streptomycin and spectinomycin
FT resistance, no ATP-binding, near wild-type streptomycin
FT binding, significantly decreased spectinomycin binding."
FT /evidence="ECO:0000269|PubMed:26527143"
FT HELIX 7..9
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 10..24
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:5LPA"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:5LPA"
FT STRAND 48..56
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 60..73
FT /evidence="ECO:0007829|PDB:5LPA"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:5LPA"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:5LPA"
FT TURN 96..99
FT /evidence="ECO:0007829|PDB:5LPA"
FT STRAND 104..109
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 114..118
FT /evidence="ECO:0007829|PDB:5LPA"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:5G4A"
FT HELIX 130..140
FT /evidence="ECO:0007829|PDB:5LPA"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 159..172
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 183..199
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 218..231
FT /evidence="ECO:0007829|PDB:5LPA"
FT HELIX 239..256
FT /evidence="ECO:0007829|PDB:5LPA"
SQ SEQUENCE 262 AA; 29348 MW; 066E1CC7E2A37977 CRC64;
MTLSIPPSIQ CQTEAACRLI TRVTGDTLRA IHLYGSAVAG GLKPNSDIDL LVTICQPLTE
AQRATLMQEL LALSSPPGAS AEKRALEVTV VLYSQLVPWC FPPSREMQFG EWLREDICQG
IYEPAQQDWD MVLLITQILE TSIPLKGERA ERLFTPAPAA QLLKALRYPL DLWQSTADVQ
GDEYHIVLTL ARIWYTLSTG RFTSKDAAAD WLLPQLPEDY AATLRAAQRE YLGLEQQDWH
ILLPAVVRFV DFAKAHIPTQ FT
