15323554

Source:http://linkedlifedata.com/resource/pubmed/id/15323554

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0005456, umls-concept:C0017725, umls-concept:C0017765, umls-concept:C0597484, umls-concept:C0598850, umls-concept:C1420200, umls-concept:C1549781, umls-concept:C2699249
pubmed:issue	34
pubmed:dateCreated	2004-8-24
pubmed:abstractText	Recently, we identified the extramembranous C-terminus loop 13 of SGLT1 as a binding site for the aromatic glucoside phlorizin, which competitively inhibits sodium D-glucose cotransport. Alkyl glucosides are also competitive inhibitors of the transport. Therefore, in this study, we searched for potential binding sites for alkyl glucosides in loop 13. To this end, we synthesized a photoaffinity label (2'-Azi-n-octyl)-beta-D-glucoside and analyzed the region of attachment using MALDI mass spectrometry, producing wild-type recombinant truncated loop 13. Furthermore, we prepared four single-Trp mutants of the loop and determined their fluorescence, its change in the presence of alkyl glucosides, and their accessibility to acrylamide. Photolabeling of truncated loop 13 with (2'-Azi-n-octyl)-beta-D-glucoside revealed an attachment of the C2 group of the alkyl chain to Gly-Phe-Phe-Arg (amino acid residues 598-601). In the presence of n-hexyl-beta-D-glucoside, all mutants (R601W, D611W, E621W, and L630W) exhibited a significant decrease in Trp fluorescence with an apparent binding affinity of 8-14 microM. Only L630W exhibited a significant blue shift, and only in R601W was a change in acrylamide quenching (protection) observed. No quenching or protection was found for D-glucose; however, 1-hexanol produced the same results as n-hexyl-beta-D-glucoside. The interaction shows stereoselectivity for n-hexyl-beta-D-glucoside binding; the beta-configuration of the sugar moiety at C1, the cis conformation of the unsaturated alkenyl side chain in the C3-C4 bond, and the alkyl chain length of six to eight carbon atoms lead to an optimum interaction. A schematic two-dimensional model was derived in which C2 interacts with the region around residue 601, C3 and C4 interact with the region between residues 614 and 619, and C6-C8 interact with the region between residues 621 and 630. The data demonstrate that loop 13 provides binding sites for alkyl glucosides as well as for phlorizin; thus, loop 13 of SGLT1 seems to be a major binding domain for the aglucone residues of competitive D-glucose transport inhibitors.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/0370623
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/1-hexanol, http://linkedlifedata.com/resource/pubmed/chemical/Acrylamide, http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Glucosides, http://linkedlifedata.com/resource/pubmed/chemical/Hexanols, http://linkedlifedata.com/resource/pubmed/chemical/Ligands, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Monosaccharide Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Photoaffinity Labels, http://linkedlifedata.com/resource/pubmed/chemical/Sodium, http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Glucose Transporter 1, http://linkedlifedata.com/resource/pubmed/chemical/Tryptophan, http://linkedlifedata.com/resource/pubmed/chemical/octyl-beta-D-glucoside
pubmed:status	MEDLINE
pubmed:month	Aug
pubmed:issn	0006-2960
pubmed:author	pubmed-author:KinneRolf K HRK, pubmed-author:KippHelmutH, pubmed-author:RajaM MobeenMM
pubmed:issnType	Print
pubmed:day	31
pubmed:volume	43
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	10944-51
pubmed:dateRevised	2006-11-15
pubmed:meshHeading	pubmed-meshheading:15323554-Acrylamide, pubmed-meshheading:15323554-Amino Acid Sequence, pubmed-meshheading:15323554-Binding, Competitive, pubmed-meshheading:15323554-Binding Sites, pubmed-meshheading:15323554-Glucose, pubmed-meshheading:15323554-Glucosides, pubmed-meshheading:15323554-Hexanols, pubmed-meshheading:15323554-Ligands, pubmed-meshheading:15323554-Membrane Glycoproteins, pubmed-meshheading:15323554-Molecular Sequence Data, pubmed-meshheading:15323554-Monosaccharide Transport Proteins, pubmed-meshheading:15323554-Mutagenesis, Site-Directed, pubmed-meshheading:15323554-Peptide Fragments, pubmed-meshheading:15323554-Photoaffinity Labels, pubmed-meshheading:15323554-Protein Structure, Secondary, pubmed-meshheading:15323554-Sodium, pubmed-meshheading:15323554-Sodium-Glucose Transporter 1, pubmed-meshheading:15323554-Spectrometry, Fluorescence, pubmed-meshheading:15323554-Stereoisomerism, pubmed-meshheading:15323554-Tryptophan
pubmed:year	2004
pubmed:articleTitle	C-terminus loop 13 of Na+ glucose cotransporter SGLT1 contains a binding site for alkyl glucosides.
pubmed:affiliation	Department of Epithelial Cell Physiology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't