Lipid A palmitoyltransferase PagP

Details

Name
Lipid A palmitoyltransferase PagP
Synonyms
  • 2.3.1.-
  • Antimicrobial peptide resistance
  • crcA
  • Lipid A acylation protein
  • ybeG
Gene Name
pagP
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0011416|Lipid A palmitoyltransferase PagP
MNVSKYVAIFSFVFIQLISVGKVFANADEWMTTFRENIAQTWQQPEHYDLYIPAITWHAR
FAYDKEKTDRYNERPWGGGFGLSRWDEKGNWHGLYAMAFKDSWNKWEPIAGYGWESTWRP
LADENFHLGLGFTAGVTARDNWNYIPLPVLLPLASVGYGPVTFQMTYIPGTYNNGNVYFA
WMRFQF
Number of residues
186
Molecular Weight
21769.475
Theoretical pI
6.52
GO Classification
Functions
O-palmitoyltransferase activity
Processes
lipid A biosynthetic process
Components
cell outer membrane / integral component of membrane
General Function
O-palmitoyltransferase activity
Specific Function
PagP is required both for biosynthesis of hepta-acylated lipid A species containing palmitate and for resistance to cationic antimicrobial peptides (CAMPs). It catalyzes the transfer of a palmitate chain (16:0) from the sn-1 position of a glycerophospholipid to the free hydroxyl group of the (R)-3-hydroxymyristate chain at position 2 of lipid A (endotoxin). Modifications of lipid A with a palmitate chain allow to evade host immune defenses by resisting antimicrobial peptides and attenuating the inflammatory response to infection triggered by lipopolysaccharide through the Toll-like receptor 4 (TLR4) signal transduction pathway. Phosphatidylglycerol (PtdGro), phosphatidylethanolamine (PtdEtn), phosphatidylserine (PtdSer) and phosphatidic acid (Ptd-OH) are all effective acyl donors.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell outer membrane
Gene sequence
>lcl|BSEQ0011417|Lipid A palmitoyltransferase PagP (pagP)
ATGAACGTGAGTAAATATGTCGCTATCTTTTCCTTTGTTTTTATTCAGTTAATCAGCGTT
GGTAAAGTTTTTGCTAACGCAGATGAGTGGATGACAACGTTTAGAGAAAATATTGCACAA
ACCTGGCAACAGCCTGAACATTATGATTTATATATTCCTGCCATCACCTGGCATGCACGT
TTCGCTTACGACAAAGAAAAAACCGATCGCTATAACGAGCGACCGTGGGGTGGCGGTTTT
GGCCTGTCGCGTTGGGATGAAAAAGGAAACTGGCATGGCCTGTATGCCATGGCATTTAAG
GACTCGTGGAACAAATGGGAACCGATTGCCGGATACGGATGGGAAAGTACCTGGCGACCG
CTGGCGGATGAAAATTTTCATTTAGGTCTGGGATTCACCGCTGGCGTAACGGCACGCGAT
AACTGGAATTACATCCCTCTCCCGGTTCTACTGCCATTGGCCTCCGTGGGTTATGGCCCA
GTGACTTTTCAGATGACCTACATTCCGGGTACCTACAACAATGGCAATGTGTACTTTGCC
TGGATGCGCTTTCAGTTTTGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP37001
UniProtKB Entry NamePAGP_ECOLI
GenBank Protein ID26986711
GenBank Gene IDS83396
General References
  1. Hu KH, Liu E, Dean K, Gingras M, DeGraff W, Trun NJ: Overproduction of three genes leads to camphor resistance and chromosome condensation in Escherichia coli. Genetics. 1996 Aug;143(4):1521-32. [Article]
  2. Oshima T, Aiba H, Baba T, Fujita K, Hayashi K, Honjo A, Ikemoto K, Inada T, Itoh T, Kajihara M, Kanai K, Kashimoto K, Kimura S, Kitagawa M, Makino K, Masuda S, Miki T, Mizobuchi K, Mori H, Motomura K, Nakamura Y, Nashimoto H, Nishio Y, Saito N, Horiuchi T, et al.: A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map. DNA Res. 1996 Jun 30;3(3):137-55. [Article]
  3. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
  4. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
  5. Bishop RE, Gibbons HS, Guina T, Trent MS, Miller SI, Raetz CR: Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria. EMBO J. 2000 Oct 2;19(19):5071-80. [Article]
  6. Guo L, Lim KB, Poduje CM, Daniel M, Gunn JS, Hackett M, Miller SI: Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell. 1998 Oct 16;95(2):189-98. [Article]
  7. Khan MA, Moktar J, Mott PJ, Vu M, McKie AH, Pinter T, Hof F, Bishop RE: Inscribing the perimeter of the PagP hydrocarbon ruler by site-specific chemical alkylation. Biochemistry. 2010 Oct 26;49(42):9046-57. doi: 10.1021/bi1011496. [Article]
  8. Hwang PM, Choy WY, Lo EI, Chen L, Forman-Kay JD, Raetz CR, Prive GG, Bishop RE, Kay LE: Solution structure and dynamics of the outer membrane enzyme PagP by NMR. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13560-5. Epub 2002 Sep 30. [Article]
  9. Ahn VE, Lo EI, Engel CK, Chen L, Hwang PM, Kay LE, Bishop RE, Prive GG: A hydrocarbon ruler measures palmitate in the enzymatic acylation of endotoxin. EMBO J. 2004 Aug 4;23(15):2931-41. Epub 2004 Jul 22. [Article]
  10. Cuesta-Seijo JA, Neale C, Khan MA, Moktar J, Tran CD, Bishop RE, Pomes R, Prive GG: PagP crystallized from SDS/cosolvent reveals the route for phospholipid access to the hydrocarbon ruler. Structure. 2010 Sep 8;18(9):1210-9. doi: 10.1016/j.str.2010.06.014. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04147Dodecyldimethylamine N-oxideexperimentalunknownDetails
DB03967Dodecyl sulfateexperimentalunknownDetails