ID   AACC3_PSEAI             Reviewed;         271 AA.
AC   P29808;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1993, sequence version 1.
DT   28-JUN-2023, entry version 65.
DE   RecName: Full=Aminoglycoside N(3)-acetyltransferase III {ECO:0000303|PubMed:1649572};
DE            EC=2.3.1.81 {ECO:0000269|PubMed:1649572, ECO:0000269|PubMed:35921328};
DE   AltName: Full=AAC(3)-IIIa {ECO:0000303|PubMed:35921328};
DE   AltName: Full=ACC(3)-III {ECO:0000303|PubMed:1649572};
DE   AltName: Full=Aminocyclitol 3-N-acetyltransferase type III;
DE   AltName: Full=Aminoglycoside acetyltransferase (3)-IIIa {ECO:0000303|PubMed:35921328};
DE   AltName: Full=Gentamicin-(3)-N-acetyl-transferase;
GN   Name=aacC3 {ECO:0000303|PubMed:1649572};
OS   Pseudomonas aeruginosa.
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Pseudomonadales;
OC   Pseudomonadaceae; Pseudomonas.
OX   NCBI_TaxID=287;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   SUBSTRATE SPECIFICITY.
RC   STRAIN=PST-I {ECO:0000303|PubMed:1649572};
RX   PubMed=1649572; DOI=10.1128/aac.35.5.892;
RA   Vliegenthart J.S., Ketelaar-Van Gaalen P.A.G., van de Klundert J.A.M.;
RT   "Nucleotide sequence of the aacC3 gene, a gentamicin resistance determinant
RT   encoding aminoglycoside-(3)-N-acetyltransferase III expressed in
RT   Pseudomonas aeruginosa but not in Escherichia coli.";
RL   Antimicrob. Agents Chemother. 35:892-897(1991).
RN   [2] {ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL, ECO:0007744|PDB:7MQM}
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH COENZYME A;
RP   GENTAMICIN; RIBOSTAMYCIN AND SISOMICIN, FUNCTION, CATALYTIC ACTIVITY,
RP   SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP   MUTAGENESIS OF TYR-64; ASP-72; GLU-123; TYR-146 AND ASP-170.
RX   PubMed=35921328; DOI=10.1371/journal.pone.0269684;
RA   Zielinski M., Blanchet J., Hailemariam S., Berghuis A.M.;
RT   "Structural elucidation of substrate-bound aminoglycoside acetyltransferase
RT   (3)-IIIa.";
RL   PLoS ONE 17:e0269684-e0269684(2022).
CC   -!- FUNCTION: Resistance to antibiotics containing the 2-deoxy-streptamine
CC       ring including dibekacin, gentamicin, kanamycin, sisomicin, tobramycin
CC       and neomycin, but not to amikacin or netilmicin (PubMed:1649572).
CC       Acetylates a broad range of both 4,5- and 4,6-disubstituted
CC       aminoglycosides, including neomycin, paromomycin, ribostamycin,
CC       sisomicin, gentamicin, tobramycin and kanamycin, with no preference of
CC       one disubstitution over the other. Acetylates sisomicin and kanamycin
CC       most and least efficiently, respectively. Does not modify plazomicin
CC       (PubMed:35921328). {ECO:0000269|PubMed:1649572,
CC       ECO:0000269|PubMed:35921328}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 2-deoxystreptamine antibiotic + acetyl-CoA = an N(3')-
CC         acetyl-2-deoxystreptamine antibiotic + CoA + H(+);
CC         Xref=Rhea:RHEA:12665, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC         ChEBI:CHEBI:57288, ChEBI:CHEBI:57921, ChEBI:CHEBI:77452; EC=2.3.1.81;
CC         Evidence={ECO:0000269|PubMed:1649572, ECO:0000269|PubMed:35921328};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12666;
CC         Evidence={ECO:0000269|PubMed:1649572, ECO:0000269|PubMed:35921328};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=6.6 uM for neomycin (at pH 6.5 and 22 degrees Celsius)
CC         {ECO:0000269|PubMed:35921328};
CC         KM=6.7 uM for paromomycin (at pH 6.5 and 22 degrees Celsius)
CC         {ECO:0000269|PubMed:35921328};
CC         KM=7.9 uM for ribostamycin (at pH 6.5 and 22 degrees Celsius)
CC         {ECO:0000269|PubMed:35921328};
CC         KM=10.9 uM for sisomicin (at pH 6.5 and 22 degrees Celsius)
CC         {ECO:0000269|PubMed:35921328};
CC         KM=10.1 uM for gentamicin (at pH 6.5 and 22 degrees Celsius)
CC         {ECO:0000269|PubMed:35921328};
CC         KM=7 uM for kanamycin (at pH 6.5 and 22 degrees Celsius)
CC         {ECO:0000269|PubMed:35921328};
CC         KM=6.6 uM for tobramycin (at pH 6.5 and 22 degrees Celsius)
CC         {ECO:0000269|PubMed:35921328};
CC         Note=kcat is 6.15 sec(-1) with neomycin as substrate. kcat is 5.52
CC         sec(-1) with paromomycin as substrate. kcat is 5.38 sec(-1) with
CC         ribostamycin as substrate. kcat is 10.48 sec(-1) with sisomicin as
CC         substrate. kcat is 8.18 sec(-1) with gentamicin as substrate. kcat is
CC         4.45 sec(-1) with kanamycin as substrate. kcat is 5.68 sec(-1) with
CC         tobramycin as substrate. {ECO:0000269|PubMed:35921328};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:35921328}.
CC   -!- SIMILARITY: Belongs to the antibiotic N-acetyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; X55652; CAA39184.1; -; Genomic_DNA.
DR   PIR; S18730; S18730.
DR   RefSeq; WP_063840261.1; NG_047241.1.
DR   PDB; 7MQK; X-ray; 1.60 A; A/B/C/D=1-271.
DR   PDB; 7MQL; X-ray; 1.60 A; A/B/C/D=1-271.
DR   PDB; 7MQM; X-ray; 1.60 A; A/B/C/D=1-271.
DR   PDB; 7Q0Q; X-ray; 1.96 A; A/B=1-269.
DR   PDB; 7Q10; X-ray; 1.82 A; A/B=1-269.
DR   PDB; 7Q1D; X-ray; 1.43 A; A/B/C/D=1-271.
DR   PDB; 7Q1X; X-ray; 1.45 A; A/B=1-271.
DR   PDBsum; 7MQK; -.
DR   PDBsum; 7MQL; -.
DR   PDBsum; 7MQM; -.
DR   PDBsum; 7Q0Q; -.
DR   PDBsum; 7Q10; -.
DR   PDBsum; 7Q1D; -.
DR   PDBsum; 7Q1X; -.
DR   AlphaFoldDB; P29808; -.
DR   SMR; P29808; -.
DR   KEGG; ag:CAA39184; -.
DR   GO; GO:0046353; F:aminoglycoside 3-N-acetyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0120225; F:coenzyme A binding; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:1901742; P:2-deoxystreptamine metabolic process; IDA:UniProtKB.
DR   GO; GO:0046356; P:acetyl-CoA catabolic process; IDA:UniProtKB.
DR   GO; GO:0016999; P:antibiotic metabolic process; IDA:UniProtKB.
DR   GO; GO:0071236; P:cellular response to antibiotic; IDA:UniProtKB.
DR   InterPro; IPR003679; Amioglycoside_AcTrfase.
DR   InterPro; IPR028345; Antibiotic_NAT-like.
DR   PANTHER; PTHR11104; AMINOGLYCOSIDE N3-ACETYLTRANSFERASE; 1.
DR   PANTHER; PTHR11104:SF0; SPBETA PROPHAGE-DERIVED AMINOGLYCOSIDE N(3')-ACETYLTRANSFERASE-LIKE PROTEIN YOKD; 1.
DR   Pfam; PF02522; Antibiotic_NAT; 1.
DR   SUPFAM; SSF110710; TTHA0583/YokD-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acyltransferase; Antibiotic resistance; Transferase.
FT   CHAIN           1..271
FT                   /note="Aminoglycoside N(3)-acetyltransferase III"
FT                   /id="PRO_0000068546"
FT   BINDING         31
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         32
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         33
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         34
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         35
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         64
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         72
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQM"
FT   BINDING         102
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQL, ECO:0007744|PDB:7MQM"
FT   BINDING         104
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         105
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         109
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         123
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         146
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         170
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQL, ECO:0007744|PDB:7MQM"
FT   BINDING         171
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQM"
FT   BINDING         173
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         176
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         212
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   BINDING         213
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQL"
FT   BINDING         221
FT                   /ligand="a 2-deoxystreptamine antibiotic"
FT                   /ligand_id="ChEBI:CHEBI:77452"
FT                   /evidence="ECO:0000269|PubMed:35921328,
FT                   ECO:0007744|PDB:7MQK, ECO:0007744|PDB:7MQL,
FT                   ECO:0007744|PDB:7MQM"
FT   MUTAGEN         64
FT                   /note="Y->F: No effect in catalytic activity with
FT                   gentamicin as substrate."
FT                   /evidence="ECO:0000269|PubMed:35921328"
FT   MUTAGEN         72
FT                   /note="D->W: No effect in catalytic activity with
FT                   gentamicin as substrate."
FT                   /evidence="ECO:0000269|PubMed:35921328"
FT   MUTAGEN         123
FT                   /note="E->F: Loss of catalytic activity with gentamicin as
FT                   substrate."
FT                   /evidence="ECO:0000269|PubMed:35921328"
FT   MUTAGEN         146
FT                   /note="Y->F: No effect in catalytic activity with
FT                   gentamicin as substrate."
FT                   /evidence="ECO:0000269|PubMed:35921328"
FT   MUTAGEN         170
FT                   /note="D->F: No effect in catalytic activity with
FT                   gentamicin as substrate."
FT                   /evidence="ECO:0000269|PubMed:35921328"
FT   HELIX           10..20
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          27..32
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           34..37
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           44..55
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   TURN            56..58
FT                   /evidence="ECO:0007829|PDB:7MQL"
FT   STRAND          59..64
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           74..76
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           79..88
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   TURN            94..96
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           101..103
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           105..111
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          126..130
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           133..137
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          142..144
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           151..157
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          161..166
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           169..171
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           174..181
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          185..198
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          201..210
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          216..218
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           221..230
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          234..239
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   STRAND          242..248
FT                   /evidence="ECO:0007829|PDB:7MQK"
FT   HELIX           249..264
FT                   /evidence="ECO:0007829|PDB:7MQK"
SQ   SEQUENCE   271 AA;  29618 MW;  A66D13D364AD1484 CRC64;
     MTDLNIPHTH AHLVDAFQAL GIRAGQALML HASVKAVGAV MGGPNVILQA LMDALTPDGT
     LMMYAGWQDI PDFIDSLPDA LKAVYLEQHP PFDPATARAV RENSVLAEFL RTWPCVHRSA
     NPEASMVAVG RQAALLTANH ALDYGYGVES PLAKLVAIEG YVLMLGAPLD TITLLHHAEY
     LAKMRHKNVV RYPCPILRDG RKVWVTVEDY DTGDPHDDYS FEQIARDYVA QGGGTRGKVG
     DADAYLFAAQ DLTRFAVQWL ESRFGDSASY G
//