Lipid II

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Lipid II
Names
Systematic IUPAC name
(2R,5R,8S,13R,16S,19R)-19-{[(2R,3R,4R,5S,6R)-3-Acetamido-5-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-2-[(1,3-dihydroxy-1,3-dioxo-3-{[(2Z,6Z,10Z,14Z,18Z,22Z,26Z,30Z,34E,38E,42E)-3,7,11,15,19,23,27,31,35,39,43-undecamethyltetratetraconta-2,6,10,14,18,22,26,30,34,38,42-undecaen-1-yl]oxy}-1λ5,3λ5-diphosphoxan-1-yl)oxy]-6-(hydroxymethyl)oxan-4-yl]oxy}-8-(4-aminobutyl)-13-carboxy-2,5,16-trimethyl-4,7,10,15,18-pentaoxo-3,6,9,14,17-pentaazaicosan-1-oic acid
Identifiers
3D model (
JSmol
)
9039417
ChEBI
ChemSpider
KEGG
  • InChI=1S/C94H156N8O26P2/c1-59(2)31-21-32-60(3)33-22-34-61(4)35-23-36-62(5)37-24-38-63(6)39-25-40-64(7)41-26-42-65(8)43-27-44-66(9)45-28-46-67(10)47-29-48-68(11)49-30-50-69(12)54-56-122-129(118,119)128-130(120,121)127-94-82(100-75(18)106)86(85(79(58-104)125-94)126-93-81(99-74(17)105)84(109)83(108)78(57-103)124-93)123-73(16)89(112)96-71(14)88(111)102-77(92(116)117)52-53-80(107)101-76(51-19-20-55-95)90(113)97-70(13)87(110)98-72(15)91(114)115/h31,33,35,37,39,41,43,45,47,49,54,70-73,76-79,81-86,93-94,103-104,108-109H,19-30,32,34,36,38,40,42,44,46,48,50-53,55-58,95H2,1-18H3,(H,96,112)(H,97,113)(H,98,110)(H,99,105)(H,100,106)(H,101,107)(H,102,111)(H,114,115)(H,116,117)(H,118,119)(H,120,121)/b60-33+,61-35+,62-37-,63-39-,64-41-,65-43-,66-45-,67-47-,68-49-,69-54-/t70-,71+,72-,73-,76+,77-,78-,79-,81-,82-,83-,84-,85-,86-,93+,94-/m1/s1 checkY
    Key: ULXTYUPMJXVUHQ-OVTFQNCVSA-N checkY
  • CC(C(=O)NC(CCC(=O)NC(CCCCN)C(=O)NC(C)C(=O)NC(C)C(=O)O)C(=O)O)NC(=O)C(C)OC1C(C(OC(C1OC2C(C(C(C(O2)CO)O)O)NC(=O)C)CO)OP(=O)(O)OP(=O)(O)OCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)NC(=O)C
Properties
C94H156N8O26P2
Molar mass 1876.23 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Lipid II is a precursor molecule in the synthesis of the

antibiotics
.

A number of analogous compounds are produced via a similar pathway in some bacteria, giving rise to cell wall modifications. See

EC 2.4.1.227 for more information.[1]

Synthesis

In peptidoglycan biosynthetic pathway

Lipid II is the final intermediate in

N-acetylmuramic acid (MurNAc), for polymerization and cross-linking into peptidoglycan. The remaining bactoprenol-pyrophosphate is then recycled to the interior of the membrane. Lipid II has been referred to as the "shuttle carrier" of peptidoglycan "building blocks'.[2]

The essential MurJ

EC 2.4.1.129) was proposed as an alternative, with evidence strongly favoring the MurJ side since 2019.[4]

Artificial production

A method for artificial production of lipid II has been described. For synthesis of lipid II from UDP-MurNAc pentapeptide and undecaprenol, the enzymes MraY, MurG, and undecaprenol kinase can be used.[5] Synthetic Lipid II analogues are used in experiments studying how it interacts with and binds molecules.[6] Significant quantities of the important peptidoglycan precursor have also be isolated, following accumulation in bacterial cells.[7]

Functions

Polymers of lipid II form a linear glycan chain. This reaction is catalyzed by the glycosyltransferases of family 51 (GT51). Transpeptidases cross link the chains and form a net-like peptidoglycan macromolecule. The resulting glycopeptide is an essential part of the envelope of many bacteria. Lipid II was estimated to exist at a concentration of less than 2000 molecules per bacterial cell.[8]

Lipid II biosynthesis is functional and essential even in organisms without a cell wall like

Chlamydia and Wolbachia. It has been hypothesized that maintaining lipid II biosynthesis reflects its role in prokaryotic cell division.[9]

In the discovery and mechanism of assembly of pili in gram positive bacteria Lipid II has been implicated as a crucial structural molecule. It anchors the pili during or after polymerization of the pilus components.[10]

Antibiotics

Since Lipid II must be flipped outside the cytoplasmic membrane before incorporation of its disaccharide-peptide unit into peptidoglycan, it is a relatively accessible target for antibiotics. These antibiotics fight bacteria by either directly inhibiting the peptidoglycan synthesis, or by binding to lipid II to form destructive pores in the cytoplasmic membrane.[11] Examples of antibiotics that target Lipid II include:

Binding

The D-Ala-D-Ala terminus is used by glycopeptide antibiotic vancomycin to inhibit lipid I- and lipid II-consuming peptidoglycan synthesis; in vancomycin-resistant strains vancomycin cannot bind, because a crucial hydrogen bond is lost. Oritavancin also uses the D-Ala-D-Ala terminus, but in addition it uses the crossbridge and D-iso-glutamine in position 2 of the lipid II stem peptide, as present in a number of Gram-positive pathogens, like staphylococci and enterococci. The increased binding of oritavancin through amidation of lipid II can compensate for the loss of a crucial hydrogen bond in vancomycin-resistant strains,[14]

Lantibiotics recognize lipid-II by its pyrophosphate.[2]

Lipid II interacts with human

Defensin, alpha 1. The latter has been used to describe and predict binding of synthetic low-molecular weight compounds created as possible therapeutic agents in treating of Gram-positive infections.[15]

Penicillin-binding protein 4 exchanges d-amino acids into Lipid II (and Lipid I), acting as a transpeptidase in vitro.[16]


References

  1. ^ "MetaCyc EC 2.4.1.227". biocyc.org.
  2. ^
    PMID 23588060
    .
  3. PMID 25013077
    .
  4. ^ "TCDB 2.A.66.4.3". tcdb.org.
  5. PMID 24990652
    .
  6. PMID 26653142
    .
  7. PMID 28553948
    .
  8. PMID 1592809
    .
  9. PMID 19656295
    .
  10. ^ Pili in Gram-positive pathogens, Nature, vol 4, pg 513
  11. ^
    PMID 18063720
    .
  12. PMID 19008088
    .
  13. S2CID 4464402
    .
  14. PMID 25403671
    .
  15. PMID 24244161
    .
  16. PMID 25291014
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Lipid_II&oldid=1188020602"