LPXC_AQUAE
ID LPXC_AQUAE Reviewed; 282 AA.
AC O67648;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=UDP-3-O-acyl-N-acetylglucosamine deacetylase {ECO:0000255|HAMAP-Rule:MF_00388};
DE Short=UDP-3-O-acyl-GlcNAc deacetylase {ECO:0000255|HAMAP-Rule:MF_00388};
DE EC=3.5.1.108 {ECO:0000255|HAMAP-Rule:MF_00388, ECO:0000269|PubMed:11148046, ECO:0000269|PubMed:15705580};
DE AltName: Full=UDP-3-O-[R-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase {ECO:0000255|HAMAP-Rule:MF_00388};
GN Name=lpxC {ECO:0000255|HAMAP-Rule:MF_00388}; Synonyms=envA;
GN OrderedLocusNames=aq_1772;
OS Aquifex aeolicus (strain VF5).
OC Bacteria; Aquificae; Aquificales; Aquificaceae; Aquifex.
OX NCBI_TaxID=224324;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VF5;
RX PubMed=9537320; DOI=10.1038/32831;
RA Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L.,
RA Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R.,
RA Feldman R.A., Short J.M., Olsen G.J., Swanson R.V.;
RT "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.";
RL Nature 392:353-358(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF HIS-19; GLU-73;
RP HIS-74; GLU-95; ASP-100; GLU-222; HIS-226; ASP-234 AND HIS-253.
RX PubMed=11148046; DOI=10.1021/bi001872g;
RA Jackman J.E., Raetz C.R., Fierke C.A.;
RT "Site-directed mutagenesis of the bacterial metalloamidase UDP-(3-O-acyl)-
RT N-acetylglucosamine deacetylase (LpxC). Identification of the zinc binding
RT site.";
RL Biochemistry 40:514-523(2001).
RN [3] {ECO:0007744|PDB:1P42}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-271 IN COMPLEX WITH ZINC.
RX PubMed=12819349; DOI=10.1073/pnas.1432990100;
RA Whittington D.A., Rusche K.M., Shin H., Fierke C.A., Christianson D.W.;
RT "Crystal structure of LpxC, a zinc-dependent deacetylase essential for
RT endotoxin biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8146-8150(2003).
RN [4] {ECO:0007744|PDB:1YH8, ECO:0007744|PDB:1YHC}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 2-271 IN COMPLEX WITH ZINC,
RP CATALYTIC ACTIVITY, AND ACTIVE SITE.
RX PubMed=15705580; DOI=10.1074/jbc.m413560200;
RA Hernick M., Gennadios H.A., Whittington D.A., Rusche K.M.,
RA Christianson D.W., Fierke C.A.;
RT "UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase functions
RT through a general acid-base catalyst pair mechanism.";
RL J. Biol. Chem. 280:16969-16978(2005).
CC -!- FUNCTION: Catalyzes the hydrolysis of UDP-3-O-myristoyl-N-
CC acetylglucosamine to form UDP-3-O-myristoylglucosamine and acetate, the
CC committed step in lipid A biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_00388, ECO:0000269|PubMed:11148046}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a UDP-3-O-[(3R)-3-hydroxyacyl]-N-acetyl-alpha-D-glucosamine +
CC H2O = a UDP-3-O-[(3R)-3-hydroxyacyl]-alpha-D-glucosamine + acetate;
CC Xref=Rhea:RHEA:67816, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:137740, ChEBI:CHEBI:173225; EC=3.5.1.108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00388,
CC ECO:0000269|PubMed:11148046, ECO:0000269|PubMed:15705580};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00388,
CC ECO:0000269|PubMed:11148046};
CC -!- PATHWAY: Glycolipid biosynthesis; lipid IV(A) biosynthesis; lipid IV(A)
CC from (3R)-3-hydroxytetradecanoyl-[acyl-carrier-protein] and UDP-N-
CC acetyl-alpha-D-glucosamine: step 2/6. {ECO:0000255|HAMAP-
CC Rule:MF_00388}.
CC -!- SIMILARITY: Belongs to the LpxC family. {ECO:0000255|HAMAP-
CC Rule:MF_00388}.
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DR EMBL; AE000657; AAC07605.1; -; Genomic_DNA.
DR PIR; F70452; F70452.
DR RefSeq; NP_214214.1; NC_000918.1.
DR RefSeq; WP_010881151.1; NC_000918.1.
DR PDB; 1P42; X-ray; 2.00 A; A/B=2-271.
DR PDB; 1XXE; NMR; -; A=1-282.
DR PDB; 1YH8; X-ray; 2.70 A; A/B=2-271.
DR PDB; 1YHC; X-ray; 2.10 A; A/B=2-271.
DR PDB; 2GO3; X-ray; 2.00 A; A/B=1-267.
DR PDB; 2GO4; X-ray; 2.70 A; A/B=1-267.
DR PDB; 2IER; X-ray; 2.70 A; A/B=1-271.
DR PDB; 2IES; X-ray; 3.10 A; A/B=1-271.
DR PDB; 2J65; X-ray; 2.20 A; A/B=1-271.
DR PDB; 2JT2; NMR; -; A=1-274.
DR PDB; 2O3Z; X-ray; 2.25 A; A/B=1-271.
DR PDB; 3P3C; X-ray; 1.25 A; A=2-275.
DR PDB; 3P76; X-ray; 1.93 A; A=1-271.
DR PDB; 4OZE; X-ray; 1.61 A; A/B=1-282.
DR PDB; 4U3B; X-ray; 1.34 A; A=1-271.
DR PDB; 4U3D; X-ray; 1.25 A; A=1-271.
DR PDB; 5DRO; X-ray; 2.01 A; A/B=1-274.
DR PDB; 5DRP; X-ray; 1.89 A; A/B=1-274.
DR PDB; 5U86; X-ray; 1.62 A; A=1-275.
DR PDB; 6IH0; X-ray; 1.21 A; A=1-271.
DR PDBsum; 1P42; -.
DR PDBsum; 1XXE; -.
DR PDBsum; 1YH8; -.
DR PDBsum; 1YHC; -.
DR PDBsum; 2GO3; -.
DR PDBsum; 2GO4; -.
DR PDBsum; 2IER; -.
DR PDBsum; 2IES; -.
DR PDBsum; 2J65; -.
DR PDBsum; 2JT2; -.
DR PDBsum; 2O3Z; -.
DR PDBsum; 3P3C; -.
DR PDBsum; 3P76; -.
DR PDBsum; 4OZE; -.
DR PDBsum; 4U3B; -.
DR PDBsum; 4U3D; -.
DR PDBsum; 5DRO; -.
DR PDBsum; 5DRP; -.
DR PDBsum; 5U86; -.
DR PDBsum; 6IH0; -.
DR AlphaFoldDB; O67648; -.
DR BMRB; O67648; -.
DR SMR; O67648; -.
DR STRING; 224324.aq_1772; -.
DR BindingDB; O67648; -.
DR ChEMBL; CHEMBL1075040; -.
DR DrugBank; DB07355; 3-(heptyloxy)benzoic acid.
DR DrugBank; DB08231; Myristic acid.
DR DrugBank; DB07536; N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}-4-{[4-(morpholin-4-ylmethyl)phenyl]ethynyl}benzamide.
DR DrugBank; DB04257; Palmitoleic Acid.
DR DrugBank; DB01991; TU-514.
DR EnsemblBacteria; AAC07605; AAC07605; aq_1772.
DR KEGG; aae:aq_1772; -.
DR PATRIC; fig|224324.8.peg.1368; -.
DR eggNOG; COG0774; Bacteria.
DR HOGENOM; CLU_046528_1_0_0; -.
DR InParanoid; O67648; -.
DR OMA; IVFYRSD; -.
DR OrthoDB; 428602at2; -.
DR BRENDA; 3.5.1.108; 396.
DR UniPathway; UPA00359; UER00478.
DR EvolutionaryTrace; O67648; -.
DR Proteomes; UP000000798; Chromosome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008759; F:UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0103117; F:UDP-3-O-acyl-N-acetylglucosamine deacetylase activity; IEA:UniProtKB-EC.
DR GO; GO:0009245; P:lipid A biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.30.1700.10; -; 1.
DR Gene3D; 3.30.230.20; -; 1.
DR HAMAP; MF_00388; LpxC; 1.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR004463; UDP-acyl_GlcNac_deAcase.
DR InterPro; IPR011334; UDP-acyl_GlcNac_deAcase_C.
DR InterPro; IPR015870; UDP-acyl_N-AcGlcN_deAcase_N.
DR PANTHER; PTHR33694; PTHR33694; 1.
DR Pfam; PF03331; LpxC; 1.
DR SUPFAM; SSF54211; SSF54211; 2.
DR TIGRFAMs; TIGR00325; lpxC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Lipid A biosynthesis; Lipid biosynthesis;
KW Lipid metabolism; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..282
FT /note="UDP-3-O-acyl-N-acetylglucosamine deacetylase"
FT /id="PRO_0000191917"
FT ACT_SITE 253
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00388,
FT ECO:0000305|PubMed:15705580"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00388,
FT ECO:0000269|PubMed:12819349, ECO:0000269|PubMed:15705580,
FT ECO:0007744|PDB:1P42, ECO:0007744|PDB:1YH8,
FT ECO:0007744|PDB:1YHC"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00388,
FT ECO:0000269|PubMed:12819349, ECO:0000269|PubMed:15705580,
FT ECO:0007744|PDB:1P42, ECO:0007744|PDB:1YH8,
FT ECO:0007744|PDB:1YHC"
FT BINDING 230
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00388,
FT ECO:0000269|PubMed:12819349, ECO:0000269|PubMed:15705580,
FT ECO:0007744|PDB:1P42, ECO:0007744|PDB:1YH8,
FT ECO:0007744|PDB:1YHC"
FT MUTAGEN 19
FT /note="H->A: 20-fold decrease in activity. 2-fold decrease
FT in zinc content."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 19
FT /note="H->Q: 2-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 19
FT /note="H->Y: 22-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 73
FT /note="E->A: 10-fold decrease in activity. 3.6-fold
FT decrease in zinc content."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 73
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 74
FT /note="H->A: Almost loss of activity. 10-fold decrease in
FT zinc content."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 74
FT /note="H->Q: Almost loss of activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 95
FT /note="E->A,N,S: Almost no change in activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 100
FT /note="D->A,N,S: Almost no change in activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 222
FT /note="E->A: 20-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 222
FT /note="E->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 222
FT /note="E->S: 15-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 226
FT /note="H->A: 720-fold decrease in activity. 16.6-fold
FT decrease in zinc content."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 234
FT /note="D->A: Almost loss of activity. 1.5-fold decrease in
FT zinc content."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 234
FT /note="D->N: 29-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 234
FT /note="D->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 253
FT /note="H->A: Loss of activity. 4.3-fold decrease in zinc
FT content."
FT /evidence="ECO:0000269|PubMed:11148046"
FT MUTAGEN 253
FT /note="H->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11148046"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 11..16
FT /evidence="ECO:0007829|PDB:6IH0"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 23..30
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 86..95
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 104..111
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:6IH0"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 183..191
FT /evidence="ECO:0007829|PDB:6IH0"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:5DRO"
FT HELIX 222..235
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:6IH0"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 253..266
FT /evidence="ECO:0007829|PDB:6IH0"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:1XXE"
SQ SEQUENCE 282 AA; 32145 MW; 38EFE076144B5F27 CRC64;
MGLEKTVKEK LSFEGVGIHT GEYSKLIIHP EKEGTGIRFF KNGVYIPARH EFVVHTNHST
DLGFKGQRIK TVEHILSVLH LLEITNVTIE VIGNEIPILD GSGWEFYEAI RKNILNQNRE
IDYFVVEEPI IVEDEGRLIK AEPSDTLEVT YEGEFKNFLG RQKFTFVEGN EEEIVLARTF
CFDWEIEHIK KVGLGKGGSL KNTLVLGKDK VYNPEGLRYE NEPVRHKVFD LIGDLYLLGS
PVKGKFYSFR GGHSLNVKLV KELAKKQKLT RDLPHLPSVQ AL
