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The N-acetyl-binding pocket of N-acetylglucosaminyltransferases also accommodates a sugar analog with a chemical handle at C2

  1. Author:
    Pasek, M.
    Ramakrishnan, B.
    Boeggeman, E.
    Mercer, N.
    Dulcey, A. E.
    Griffiths, G. L.
    Qasba, P. K.
  2. Author Address

    [Pasek, Marta; Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Mercer, Natalia; Qasba, Pradman K.] NCI Frederick, Struct Glycobiol Sect, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. [Ramakrishnan, Boopathy; Boeggeman, Elizabeth] NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21702 USA. [Dulcey, Andres E.; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.;Qasba, PK (reprint author), NCI Frederick, Struct Glycobiol Sect, Ctr Canc Res, Nanobiol Program, Bldg 469,Room 221, Frederick, MD 21702 USA;qasba@helix.nih.gov
    1. Year: 2012
    2. Date: Mar
  1. Journal: Glycobiology
    1. 22
    2. 3
    3. Pages: 379-388
  2. Type of Article: Article
  3. ISSN: 0959-6658
  1. Abstract:

    In recent years, sugars with a unique chemical handle have been used to detect and elucidate the function of glycoconjugates. Such chemical handles have generally been part of an N-acetyl moiety of a sugar. We have previously developed several applications using the single mutant Y289L-beta 1,4-galactosyltransferase I (Y289L-beta 4Gal-T1) and the wild-type polypeptide-alpha-GalNAc-T enzymes with UDP-C2-keto-Gal. Here, we describe for the first time that the GlcNAc-transferring enzymes-R228K-Y289L-beta 4Gal-T1 mutant enzyme, the wild-type human beta 1,3-N-acetylglucosaminyltransferase-2 and human Maniac Fringe-can also transfer the GlcNAc analog C2-keto-Glc molecule from UDP-C2-keto-Glc to their respective acceptor substrates. Although the R228K-Y289L-beta 4Gal-T1 mutant enzyme transfers the donor sugar substrate GlcNAc or its analog C2-keto-Glc only to its natural acceptor substrate, GlcNAc, it does not transfer to its analog C2-keto-Glc. Thus, these observations suggest that the GlcNAc-transferring glycosyltransferases can generally accommodate a chemical handle in the N-acetyl-binding cavity of the donor sugar substrate, but not in the N-acetyl-binding cavity of the acceptor sugar.

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External Sources

  1. DOI: 10.1093/glycob/cwr110
  2. WOS: 000299747400008

Library Notes

  1. Fiscal Year: FY2011-2012
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