ARNA_SALTY
ID ARNA_SALTY Reviewed; 660 AA.
AC O52325;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Bifunctional polymyxin resistance protein ArnA;
DE Includes:
DE RecName: Full=UDP-4-amino-4-deoxy-L-arabinose formyltransferase;
DE EC=2.1.2.13;
DE AltName: Full=ArnAFT;
DE AltName: Full=UDP-L-Ara4N formyltransferase;
DE Includes:
DE RecName: Full=UDP-glucuronic acid oxidase, UDP-4-keto-hexauronic acid decarboxylating;
DE EC=1.1.1.305;
DE AltName: Full=ArnADH;
DE AltName: Full=UDP-GlcUA decarboxylase;
DE AltName: Full=UDP-glucuronic acid dehydrogenase;
GN Name=arnA; Synonyms=pbgP3, pmrI; OrderedLocusNames=STM2299;
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 [GENOMIC DNA].
RC STRAIN=ATCC 14028s / SGSG 2262;
RX PubMed=9570402; DOI=10.1046/j.1365-2958.1998.00757.x;
RA Gunn J.S., Lim K.B., Krueger J., Kim K., Guo L., Hackett M., Miller S.I.;
RT "PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A
RT modification and polymyxin resistance.";
RL Mol. Microbiol. 27:1171-1182(1998).
RN [2]
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 [3]
RP INDUCTION.
RC STRAIN=ATCC 14028s / SGSG 2262;
RX PubMed=10480935; DOI=10.1074/jbc.274.38.27185;
RA Woesten M.M.S.M., Groisman E.A.;
RT "Molecular characterization of the PmrA regulon.";
RL J. Biol. Chem. 274:27185-27190(1999).
RN [4]
RP INDUCTION BY BASR.
RX PubMed=15569938; DOI=10.1073/pnas.0406038101;
RA Winfield M.D., Groisman E.A.;
RT "Phenotypic differences between Salmonella and Escherichia coli resulting
RT from the disparate regulation of homologous genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17162-17167(2004).
CC -!- FUNCTION: Bifunctional enzyme that catalyzes the oxidative
CC decarboxylation of UDP-glucuronic acid (UDP-GlcUA) to UDP-4-keto-
CC arabinose (UDP-Ara4O) and the addition of a formyl group to UDP-4-
CC amino-4-deoxy-L-arabinose (UDP-L-Ara4N) to form UDP-L-4-formamido-
CC arabinose (UDP-L-Ara4FN). The modified arabinose is attached to lipid A
CC and is required for resistance to polymyxin and cationic antimicrobial
CC peptides (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + UDP-alpha-D-glucuronate = CO2 + NADH + UDP-beta-L-
CC threo-pentopyranos-4-ulose; Xref=Rhea:RHEA:24702, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58710; EC=1.1.1.305;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-10-formyltetrahydrofolate + UDP-4-amino-4-deoxy-beta-L-
CC arabinose = (6S)-5,6,7,8-tetrahydrofolate + H(+) + UDP-4-deoxy-4-
CC formamido-beta-L-arabinose; Xref=Rhea:RHEA:24706, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57453, ChEBI:CHEBI:57454, ChEBI:CHEBI:58708,
CC ChEBI:CHEBI:58709; EC=2.1.2.13;
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; UDP-4-deoxy-4-formamido-beta-L-
CC arabinose biosynthesis; UDP-4-deoxy-4-formamido-beta-L-arabinose from
CC UDP-alpha-D-glucuronate: step 1/3.
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; UDP-4-deoxy-4-formamido-beta-L-
CC arabinose biosynthesis; UDP-4-deoxy-4-formamido-beta-L-arabinose from
CC UDP-alpha-D-glucuronate: step 3/3.
CC -!- PATHWAY: Bacterial outer membrane biogenesis; lipopolysaccharide
CC biosynthesis.
CC -!- SUBUNIT: Homohexamer, formed by a dimer of trimers. {ECO:0000250}.
CC -!- INDUCTION: Induced by BasR. {ECO:0000269|PubMed:10480935,
CC ECO:0000269|PubMed:15569938}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the Fmt family. UDP-
CC L-Ara4N formyltransferase subfamily. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NAD(P)-dependent
CC epimerase/dehydratase family. UDP-glucuronic acid decarboxylase
CC subfamily. {ECO:0000305}.
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DR EMBL; AF036677; AAC04772.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL21200.1; -; Genomic_DNA.
DR RefSeq; NP_461241.1; NC_003197.2.
DR RefSeq; WP_000648776.1; NC_003197.2.
DR AlphaFoldDB; O52325; -.
DR SMR; O52325; -.
DR STRING; 99287.STM2299; -.
DR PaxDb; O52325; -.
DR EnsemblBacteria; AAL21200; AAL21200; STM2299.
DR GeneID; 1253821; -.
DR KEGG; stm:STM2299; -.
DR PATRIC; fig|99287.12.peg.2434; -.
DR HOGENOM; CLU_007383_23_2_6; -.
DR OMA; VRYCVKY; -.
DR PhylomeDB; O52325; -.
DR BioCyc; SENT99287:STM2299-MON; -.
DR UniPathway; UPA00030; -.
DR UniPathway; UPA00032; UER00492.
DR UniPathway; UPA00032; UER00494.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0016831; F:carboxy-lyase activity; IEA:InterPro.
DR GO; GO:0099619; F:UDP-4-amino-4-deoxy-L-arabinose formyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0099618; F:UDP-glucuronic acid dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0009245; P:lipid A biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009103; P:lipopolysaccharide biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR CDD; cd05257; Arna_like_SDR_e; 1.
DR HAMAP; MF_01166; ArnA; 1.
DR InterPro; IPR045869; Arna-like_SDR_e.
DR InterPro; IPR021168; Bifun_polymyxin_resist_ArnA.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR005793; Formyl_trans_C.
DR InterPro; IPR002376; Formyl_transf_N.
DR InterPro; IPR036477; Formyl_transf_N_sf.
DR InterPro; IPR011034; Formyl_transferase-like_C_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01370; Epimerase; 1.
DR Pfam; PF02911; Formyl_trans_C; 1.
DR Pfam; PF00551; Formyl_trans_N; 1.
DR PIRSF; PIRSF036506; Bifun_polymyxin_resist_ArnA; 1.
DR SUPFAM; SSF50486; SSF50486; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53328; SSF53328; 1.
PE 2: Evidence at transcript level;
KW Antibiotic resistance; Lipid A biosynthesis; Lipid biosynthesis;
KW Lipid metabolism; Lipopolysaccharide biosynthesis; Multifunctional enzyme;
KW NAD; Oxidoreductase; Reference proteome; Transferase.
FT CHAIN 1..660
FT /note="Bifunctional polymyxin resistance protein ArnA"
FT /id="PRO_0000083109"
FT REGION 1..304
FT /note="Formyltransferase ArnAFT"
FT REGION 314..660
FT /note="Dehydrogenase ArnADH"
FT ACT_SITE 104
FT /note="Proton donor; for formyltransferase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 434
FT /note="Proton acceptor; for decarboxylase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 619
FT /note="Proton donor; for decarboxylase activity"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250"
FT BINDING 136..140
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250"
FT BINDING 347
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 368..369
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 393
FT /ligand="UDP-alpha-D-glucuronate"
FT /ligand_id="ChEBI:CHEBI:58052"
FT /evidence="ECO:0000250"
FT BINDING 398
FT /ligand="UDP-alpha-D-glucuronate"
FT /ligand_id="ChEBI:CHEBI:58052"
FT /evidence="ECO:0000250"
FT BINDING 432..433
FT /ligand="UDP-alpha-D-glucuronate"
FT /ligand_id="ChEBI:CHEBI:58052"
FT /evidence="ECO:0000250"
FT BINDING 460
FT /ligand="UDP-alpha-D-glucuronate"
FT /ligand_id="ChEBI:CHEBI:58052"
FT /evidence="ECO:0000250"
FT BINDING 492
FT /ligand="UDP-alpha-D-glucuronate"
FT /ligand_id="ChEBI:CHEBI:58052"
FT /evidence="ECO:0000250"
FT BINDING 526..535
FT /ligand="UDP-alpha-D-glucuronate"
FT /ligand_id="ChEBI:CHEBI:58052"
FT /evidence="ECO:0000250"
FT BINDING 613
FT /ligand="UDP-alpha-D-glucuronate"
FT /ligand_id="ChEBI:CHEBI:58052"
FT /evidence="ECO:0000250"
FT SITE 102
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 140
FT /note="Raises pKa of active site His"
FT /evidence="ECO:0000250"
SQ SEQUENCE 660 AA; 73588 MW; 49151B1883EB1157 CRC64;
MKAVIFAYHD MGCQGVQAVL DAGYEIAAIF THADNPAENT FFGSVSRQAA ELGIPVYAPD
NVNHPIWVDR IAELAPDIIF SFYYRNLLSE EILHLAPAGA FNLHGSLLPA YRGRAPLNWV
LVNGESETGV TLHRMVKRAD AGEIVASQRV AIAQDDVALT LHHKLCQAAR QLLNSILPTM
KCGDIPSVPQ RESDSTYYGR RRPEDGLIDW HKPVSTVHNL VRAVAAPWPG AFSYNGSQKF
TIWSSRMCPD AQGALPGSVI SVSPLRVACA DGALEIITGQ AGDDITVQGS QLAQTLGLVA
GARLNRPPAT SGKRRIRVLI LGVNGFIGNH LTERLLNEEN YEVYGMDIGS NAISRFLLHP
RFHFVEGDIS IHSEWIEYHV KKCDVVLPLV AIATPIEYTR NPLRVFELDF EENLRIIRYC
VKYRKRVVFP STSEVYGMCT DASFDEDKSN LIVGPVNKPR WIYSVSKQLL DRVIWAYGEK
EGLRFTLFRP FNWMGPRLDS LNAARIGSSR AITQLILNLV EGTPIKLIDG GQQKRCFTDI
RDGIEALFRI IVNDGDRCDG KIINIGNPDN EASIQELATL LLDSFDKHPL RCHFPPFAGF
QVVESRSYYG KGYQDVAHRK PSIDNARRCL GWEPSIAMRD TVEETLDFFL RSVDIAERAS
