ID A0A085GAK7_EWIA3 Unreviewed; 660 AA. AC A0A085GAK7; DT 29-OCT-2014, integrated into UniProtKB/TrEMBL. DT 29-OCT-2014, sequence version 1. DT 02-OCT-2024, entry version 52. DE RecName: Full=Bifunctional polymyxin resistance protein ArnA {ECO:0000256|HAMAP-Rule:MF_01166}; DE Includes: DE RecName: Full=UDP-4-amino-4-deoxy-L-arabinose formyltransferase {ECO:0000256|HAMAP-Rule:MF_01166}; DE EC=2.1.2.13 {ECO:0000256|HAMAP-Rule:MF_01166}; DE AltName: Full=ArnAFT {ECO:0000256|HAMAP-Rule:MF_01166}; DE AltName: Full=UDP-L-Ara4N formyltransferase {ECO:0000256|HAMAP-Rule:MF_01166}; DE Includes: DE RecName: Full=UDP-glucuronic acid oxidase, UDP-4-keto-hexauronic acid decarboxylating {ECO:0000256|HAMAP-Rule:MF_01166}; DE EC=1.1.1.305 {ECO:0000256|HAMAP-Rule:MF_01166}; DE AltName: Full=ArnADH {ECO:0000256|HAMAP-Rule:MF_01166}; DE AltName: Full=UDP-GlcUA decarboxylase {ECO:0000256|HAMAP-Rule:MF_01166}; DE AltName: Full=UDP-glucuronic acid dehydrogenase {ECO:0000256|HAMAP-Rule:MF_01166}; GN Name=arnA {ECO:0000256|HAMAP-Rule:MF_01166}; GN ORFNames=GEAM_2074 {ECO:0000313|EMBL:KFC80752.1}; OS Ewingella americana (strain ATCC 33852 / DSM 4580 / CCUG 14506 / JCM 5911 / OS LMG 7869 / NCTC 12157 / CDC 1468-78). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Yersiniaceae; Ewingella. OX NCBI_TaxID=910964 {ECO:0000313|EMBL:KFC80752.1, ECO:0000313|Proteomes:UP000028640}; RN [1] {ECO:0000313|EMBL:KFC80752.1, ECO:0000313|Proteomes:UP000028640} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 33852 {ECO:0000313|EMBL:KFC80752.1, RC ECO:0000313|Proteomes:UP000028640}; RA Plunkett G.III., Neeno-Eckwall E.C., Glasner J.D., Perna N.T.; RT "ATOL: Assembling a taxonomically balanced genome-scale reconstruction of RT the evolutionary history of the Enterobacteriaceae."; RL Submitted (MAY-2014) to the EMBL/GenBank/DDBJ databases. 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. {ECO:0000256|HAMAP-Rule:MF_01166}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-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:58708, ChEBI:CHEBI:58709, CC ChEBI:CHEBI:195366; EC=2.1.2.13; Evidence={ECO:0000256|HAMAP- CC Rule:MF_01166}; 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; Evidence={ECO:0000256|HAMAP- CC Rule:MF_01166}; CC -!- PATHWAY: Bacterial outer membrane biogenesis; lipopolysaccharide CC biosynthesis. {ECO:0000256|HAMAP-Rule:MF_01166}. 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. {ECO:0000256|HAMAP-Rule:MF_01166}. 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. {ECO:0000256|HAMAP-Rule:MF_01166}. CC -!- SUBUNIT: Homohexamer, formed by a dimer of trimers. {ECO:0000256|HAMAP- CC Rule:MF_01166}. CC -!- SIMILARITY: In the C-terminal section; belongs to the NAD(P)-dependent CC epimerase/dehydratase family. UDP-glucuronic acid decarboxylase CC subfamily. {ECO:0000256|HAMAP-Rule:MF_01166}. CC -!- SIMILARITY: In the N-terminal section; belongs to the Fmt family. UDP- CC L-Ara4N formyltransferase subfamily. {ECO:0000256|HAMAP-Rule:MF_01166}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_01166}. CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:KFC80752.1}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; JMPJ01000053; KFC80752.1; -; Genomic_DNA. DR RefSeq; WP_034791177.1; NZ_JMPJ01000053.1. DR AlphaFoldDB; A0A085GAK7; -. DR STRING; 910964.GEAM_2074; -. DR GeneID; 78380414; -. DR eggNOG; COG0223; Bacteria. DR eggNOG; COG0451; Bacteria. DR OrthoDB; 9802815at2; -. DR UniPathway; UPA00030; -. DR UniPathway; UPA00032; UER00492. DR Proteomes; UP000028640; Unassembled WGS sequence. 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-UniRule. DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW. DR CDD; cd08702; Arna_FMT_C; 1. DR CDD; cd05257; Arna_like_SDR_e; 1. DR Gene3D; 3.40.50.12230; -; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 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; IPR050177; Lipid_A_modif_metabolic_enz. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR PANTHER; PTHR43245; BIFUNCTIONAL POLYMYXIN RESISTANCE PROTEIN ARNA; 1. DR PANTHER; PTHR43245:SF13; NAD(P)-BD_DOM DOMAIN-CONTAINING PROTEIN; 1. 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; FMT C-terminal domain-like; 1. DR SUPFAM; SSF53328; Formyltransferase; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. PE 3: Inferred from homology; KW Antibiotic resistance {ECO:0000256|ARBA:ARBA00023251, ECO:0000256|HAMAP- KW Rule:MF_01166}; KW Lipid A biosynthesis {ECO:0000256|ARBA:ARBA00022556, ECO:0000256|HAMAP- KW Rule:MF_01166}; KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516, ECO:0000256|HAMAP- KW Rule:MF_01166}; KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098, ECO:0000256|HAMAP- KW Rule:MF_01166}; KW Lipopolysaccharide biosynthesis {ECO:0000256|ARBA:ARBA00022985, KW ECO:0000256|HAMAP-Rule:MF_01166}; Lyase {ECO:0000313|EMBL:KFC80752.1}; KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268, ECO:0000256|HAMAP- KW Rule:MF_01166}; KW NAD {ECO:0000256|ARBA:ARBA00023027, ECO:0000256|HAMAP-Rule:MF_01166}; KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002, ECO:0000256|HAMAP- KW Rule:MF_01166}; Reference proteome {ECO:0000313|Proteomes:UP000028640}; KW Transferase {ECO:0000256|HAMAP-Rule:MF_01166, ECO:0000313|EMBL:KFC80752.1}. FT DOMAIN 56..177 FT /note="Formyl transferase N-terminal" FT /evidence="ECO:0000259|Pfam:PF00551" FT DOMAIN 203..284 FT /note="Formyl transferase C-terminal" FT /evidence="ECO:0000259|Pfam:PF02911" FT DOMAIN 318..566 FT /note="NAD-dependent epimerase/dehydratase" FT /evidence="ECO:0000259|Pfam:PF01370" FT REGION 1..304 FT /note="Formyltransferase ArnAFT" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT REGION 314..660 FT /note="Dehydrogenase ArnADH" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT ACT_SITE 104 FT /note="Proton donor; for formyltransferase activity" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT ACT_SITE 434 FT /note="Proton acceptor; for decarboxylase activity" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT ACT_SITE 619 FT /note="Proton donor; for decarboxylase activity" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 114 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 136..140 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 347 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 368..369 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 393 FT /ligand="UDP-alpha-D-glucuronate" FT /ligand_id="ChEBI:CHEBI:58052" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 398 FT /ligand="UDP-alpha-D-glucuronate" FT /ligand_id="ChEBI:CHEBI:58052" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 432..433 FT /ligand="UDP-alpha-D-glucuronate" FT /ligand_id="ChEBI:CHEBI:58052" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 460 FT /ligand="UDP-alpha-D-glucuronate" FT /ligand_id="ChEBI:CHEBI:58052" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 492 FT /ligand="UDP-alpha-D-glucuronate" FT /ligand_id="ChEBI:CHEBI:58052" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 526..535 FT /ligand="UDP-alpha-D-glucuronate" FT /ligand_id="ChEBI:CHEBI:58052" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT BINDING 613 FT /ligand="UDP-alpha-D-glucuronate" FT /ligand_id="ChEBI:CHEBI:58052" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT SITE 102 FT /note="Transition state stabilizer" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" FT SITE 140 FT /note="Raises pKa of active site His" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01166" SQ SEQUENCE 660 AA; 74119 MW; 2F5C877736ED6566 CRC64; MKAIVFAYHD IGCVGLQALV DAGYDVQAVF THTDSPDENN FFSSVARVGA GLNLPVYAPE DVNHPLWVDR IRELQPDVIF SFYYRNMLSE EVLSLAPLGG FNLHGSLLPR YRGRAPVNWA LLKGETETGV TLHKMVKRPD AGDIVGQLAV PISNDDIALT LHAKVRDAAK VLLTDVLPKI KQGNVTLTPQ DESQASYFGR RTAADGEIHW HKSATEINNL IRAVTEPYPG AFTYLGQRKM TIWRSRPLDT AHDKKPGTVL SSDPLVVACG TGALEILAGQ SESGLYVQGS RLALELGIMP DVKLSSLPTA VMKRRTRVLI LGVNGFIGNH LSERLLREDN YEIFGLDISS DAVSRFMDNP HFHFVEGDIS IHSEWIEYHI KKCDVILPLV AIATPIEYTR NPLRVFELDF EENLKIVRDC VKYKKRIIFP STSEVYGMCD DKEFDEDTSR LIVGPINKQR WIYSVSKQLL DRVIWAYGVK EGLRFTLFRP FNWMGPRLDN LDAARIGSSR AITQLILNLV EGSPIKLVDG GEQKRTFTDI TDGIEALFRI VENKEDRCDG QIINIGNPTN EASIRELAEM LLRSFEAHPL RDQFPPFAGF KSVESSTYYG KGYQDVEHRT PSIKNAKRLL GWTPEIAMDK TVEKTLDFFL RSVNPDNNQA //