Arabinogalactan

Arabinogalactan is a biopolymer consisting of arabinose and galactose monosaccharides. Two classes of arabinogalactans are found in nature: plant arabinogalactan and microbial arabinogalactan. In plants, it is a major constituent of many gums, including gum arabic and gum gutti. It is often found attached to proteins, and the resulting arabinogalactan protein (AGP) functions as a signaling molecule between cells and a glue to seal wounds of plants.[1]

The microbial arabinogalactan is a major structural component of the mycobacterial cell wall.[2][3] Both the arabinose and galactose are solely in the furanose configuration. The galactan portion of the microbial arabinogalactan is linear, consisting of approximately 30 units with alternating β-(1-5) and β-(1-6) glycosidic linkages. The arabinan chain, which consist of about 30 residues,[4] is attached at three branch points within the galactan chain (believed to be at residues 8, 10 and 12).[5] The arabinan portion of the polymer is a complex branched structure, usually capped with mycolic acids. The arabinan glycosidic linkages are α-(1-3), α-(1-5), and β-(1-2).

Structure of microbial arabinogalactan

The reducing end of micobacterial arabinogalactan consists of the terminal sequence →5)-D-Galf-(1→4)-L-Rhap-(1→3)-D-GlcNAc. A muramyl-6-P was also found within the peptidoglycan functional group. The mycolylarabinogalactan of mycobacteria is attached to the peptidoglycan by the actinomycete-specific diglycosylphosphoryl bridge, L-Rhap-(1→3)-D-GlcNAc-(1→P).[3]

Arabinogalactan contains a galactan chain, with alternating 5-linked β-D-galactofuranosyl (Galf) and 6-linked β-D-Galf residues. The arabinan chains are attached to C-5 of some of the 6-linked Galf residues. There are three major structural domains for arabinan;

  1. A domain consisting of linear 5-linked α-D-Araf residues.
  2. A domain with branched 3,5 linked α-D-Araf residues substituted with 5-linked α-D-Araf units at both branched positions.
  3. A terminal non-reducing domain for end arabinan consisting of a 3,5-linked α-D-Araf residue substituted at both branched positions with the disaccharide β-D Araf-(1→2)- α-D-Araf.

These three arabinan chains are attached to the galactan at residues 8, 10, and 12.[3]

The non-reducing end of arabinogalactan is covalently attached to the mycolic acids of the outer membrane. The hydrophobicity of mycolic acids is a barrier to drug entry. Additionally, the mycolyl arabinogalactan peptidiglycan is responsible for aspects of disease pathogenesis and much of the antibody response in infections. The mycolyl substituents are selectively and equally distributed on the 5-hydroxyl functions of terminal- and the penultimate 2-linked Araf residues. The mycolyl residues are clustered in groups of four on the non reducing terminal pentaarabinosyl unit (β-Araf-(1→2)-α-Araf)2-3,5-α-Araf . Thus, the major part (66%) of the pentaarabinosyl units are substituted by mycolic acids, leaving the unsubstituted minor region (33%), that is available for interaction with the immune system.[3]

Approximately one of the three arabinosyl chains attached to the galactan chain containing succinyl groups. Although one succinyl group is most common, up to three succinyl groups per released arabinan fragment can be found on oligo-arabinans. However, arabinan fragments substituted with GalNH2 are not succinylated. Importantly, in the case of M. tuberculosis, and most likely in all slow growers, both positive charge (protonated GalNH2 as GalNH3+) and negative charge (succinyl) are present in the middle regions of the arabinan, specifically at O-2 of the inner 3,5-α-D-Araf units. The succinyl residues are on the non-mycolylated chain. Recently a complete primary model of arabinogalactan has been proposed.[3]

See also

References

  1. ^ Nothnagel EA, Bacic A, Clarke AE (2000). Cell and developmental biology of arabinogalactan-proteins. Kluwer Academic/Plenum Publishers. ISBN 0-306-4649-1. 
  2. ^ Esko, Jeffrey D.; Tamara L. Doering, and Christian R.H. Raetz (2008). in Essentials of Glycobiology. Cold Spring Harbor Press. pp. Ch. 20. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=glyco2. 
  3. ^ a b c d e Bhamidi S (2009). "Mycobacterial Cell Wall Arabinogalactan". Bacterial Polysaccharides: Current Innovations and Future Trends. Caister Academic Press. ISBN 978-1-904455-45-5. 
  4. ^ Suresh Bhamidi, Michael S. Scherman, Christopher D. Rithner, Jessica E. Prenni, Delphi Chatterjee, Kay-Hooi Khoo, and Michael R. McNeil Journal of Biological Chemistry, 2008, 283, 12992-13000
  5. ^ Luke J. Alderwick, Eva Radmacher, Mathias Seidel, Roland Gande, Paul G. Hitchen, Howard R. Morris, Anne Dell, Hermann Sahm, Lothar Eggeling, Gurdyal S. Besra Journal of Biological Chemistry, 2005, 280, 32362-32371
Pathogenic bacteria
Human flora
Substrate preference
Oxygen preference
Structures
Outside envelope
Composite
Shapes

M: BAC

bact (clas)

gr+f/gr+a(t)/gr-p(c)/gr-o

drug(J1p, w, n, m, vacc)