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Specificity of GDP‐Man:dolichyl‐phosphate mannosyltransferase for the guanosine diphosphate esters of mannose analogues containing deoxy and deoxyfluoro substituents
Author(s) -
McDowell William,
Schwarz Ralph T.
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)80173-5
Subject(s) - chemistry , mannose , guanosine , guanosine diphosphate , biochemistry , mannose 6 phosphate , stereochemistry , receptor , enzyme , gtp' , guanosine triphosphate , growth factor
Guanosine diphosphate (GDP) esters of 2‐deoxy‐D‐glucose (2dGlc), 2‐deoxy‐2‐fluoro‐D‐mannose (2FMan), 3‐deoxy‐D‐mannose (3dMan), 4‐deoxy‐D‐mannose (4dMan) and 6‐deoxy‐D‐mannose (6dMan) have been synthesised and tested for their ability to act as inhibitors of dolichyl phosphate mannose synthesis (enzyme: GDP‐mannose:dolichyl‐phosphate mannosyltransferase, EC 2.4.1.83) in chick embryo cell microsomal membranes. The following order of efficiency was found with the apparent K i in parentheses: GDP‐6dMan (0.40 μM±0.15) > GDP‐3dMan (1.0 μM±0.1) = GDP‐2dGlc (1.3 μM±0.2) > GDP‐4dMan (3.1 μM±0.1) GDP‐2FMan (15 μM±0). For comparison the K m for GDP‐Man was 0.52 μM±0.02 and the K i for GDP was 56 μM±2. These results indicate that the 6‐hydroxyl group of mannose is not crucial for emzyme‐substrate recognition, whereas the 2‐ and 3‐hydroxyls may have some involvement. The 4‐hydroxyl appears to be an important determinant for enzyme‐substrate recognition in this mannosyltransferase.