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Differential chemical modification of substrate binding areas in porcine-pancreatic alpha-amylase by three regioisomeric photolabile ligands

✍ Scribed by Jochen Lehmann; Guy Marchis-Mouren; Emile Schiltz; Markus Schmidt-Schuchardt


Book ID
102995038
Publisher
Elsevier Science
Year
1994
Tongue
English
Weight
882 KB
Volume
265
Category
Article
ISSN
0008-6215

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✦ Synopsis


Three regioisomeric radiolabelled spacer-modified oligosaccharides: methyl 4'-0-[4-S-(3-azi-4-~-~-glucopyranosyloxy-l-~3H]butyl)-6-deoxy-4-thio-cY-~-xylo-hex-S-enopyranosyl]-~-mal~oside (12a, Gl-G3*), methyl 4-0-[4-S-(3-azi-4-cr-maltosyloxy-l-[3H~utyl)-6-deoxy-4-tio-~-D-xylohexd-enopyranosyl]-a-D-glucopyranoside (15a, G2-G2*) and methyl 4-S-(3-azi-4-a-maltotriosyloxy-1-[ 3Hlbutyl)-4-deoxy-4-thio-~-DxyZo-hex-5-enopyranoside (16a, G3-Cl*) were synthesised and used as photoaffinity probes for the chemical modification of porcine-pancreatic alpha-amylase (PPA). Incorporation of covalently attached radioactivity amounted to 25-38% of the stoichiometric value. Tryptic digestion of the three labelled protein preparations PPA-Gl-G3*, PPA-G2-G2*, and PPA-G3-Gl* and the purification of the labelled peptides by fractional HPLC yielded altogether six pure components. On the basis of the published three-dimensional structure peptides Gl-G3-II, G2-G2-II, and G2-G2-III were part of the catalytic site. Gl-G3-I and G2-G2-I were part of the surface binding site. The major component derived from PPA, labelled by G3-Cl*, corresponded to an area that is neither close to the active site nor to the surface starch-binding domain, which clearly indicates the presence of a third, hitherto undetected, substrate-binding site.