Determination of the solution conformation of D-gluco-dihydroacarbose, a high-affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy

Thomas Weimar; Bent O. Petersen; Birte Svensson; B. Mario Pinto

doi:10.1016/S0008-6215(00)00021-5

Determination of the solution conformation of D-gluco-dihydroacarbose, a high-affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy

Thomas Weimar^*, Bent O. Petersen, Birte Svensson, B. Mario Pinto

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Chemie und Metabolomics

9 Zitate (Scopus)

Abstract

The determination of the bound solution conformation of D-gluco- dihydroacarbose (GAC), a tight-binding inhibitor of several glycosidase and amylase enzymes, by glucoamylase is described. Transferred NOE NMR experiments and line-broadening effects indicate that GAC is bound in a conformation resembling that observed in the crystal structure. This contrasts with the predominant conformation of GAC when free in solution. The NMR results also suggest regions on the carbohydrate that are in close contact with the protein. The determination of the bound solution conformation of GAC by glucoamylase using transferred NOE (trNOE) measurements is a significant achievement given the high affinity constant (K(a) = 3 x 10⁷ M^-1) for this receptor-ligand pair. It is striking that the off-rate for complexation is still sufficiently high to permit observation of trNOEs. (C) 2000 Elsevier Science Ltd.

Originalsprache	Englisch
Zeitschrift	Carbohydrate Research
Jahrgang	326
Ausgabenummer	1
Seiten (von - bis)	50-55
Seitenumfang	6
ISSN	0008-6215
DOIs	https://doi.org/10.1016/S0008-6215(00)00021-5
Publikationsstatus	Veröffentlicht - 19.05.2000

Fördermittel

This work was supported with grants from the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industry (to T.W.), NATO (CRG #931165), and the Natural Sciences and Engineering Research Council of Canada. We are also grateful to K. Bock and M. Meldal for the gift of GAC.

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Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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10.1016/S0008-6215(00)00021-5

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title = "Determination of the solution conformation of D-gluco-dihydroacarbose, a high-affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy",

abstract = "The determination of the bound solution conformation of D-gluco- dihydroacarbose (GAC), a tight-binding inhibitor of several glycosidase and amylase enzymes, by glucoamylase is described. Transferred NOE NMR experiments and line-broadening effects indicate that GAC is bound in a conformation resembling that observed in the crystal structure. This contrasts with the predominant conformation of GAC when free in solution. The NMR results also suggest regions on the carbohydrate that are in close contact with the protein. The determination of the bound solution conformation of GAC by glucoamylase using transferred NOE (trNOE) measurements is a significant achievement given the high affinity constant (K(a) = 3 x 107 M-1) for this receptor-ligand pair. It is striking that the off-rate for complexation is still sufficiently high to permit observation of trNOEs. (C) 2000 Elsevier Science Ltd.",

author = "Thomas Weimar and Petersen, \{Bent O.\} and Birte Svensson and Pinto, \{B. Mario\}",

note = "Funding Information: This work was supported with grants from the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industry (to T.W.), NATO (CRG \#931165), and the Natural Sciences and Engineering Research Council of Canada. We are also grateful to K. Bock and M. Meldal for the gift of GAC. Copyright: Copyright 2007 Elsevier B.V., All rights reserved.",

year = "2000",

month = may,

day = "19",

doi = "10.1016/S0008-6215(00)00021-5",

language = "English",

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journal = "Carbohydrate Research",

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Determination of the solution conformation of D-gluco-dihydroacarbose, a high-affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy. / Weimar, Thomas; Petersen, Bent O.; Svensson, Birte et al.
in: Carbohydrate Research, Jahrgang 326, Nr. 1, 19.05.2000, S. 50-55.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Determination of the solution conformation of D-gluco-dihydroacarbose, a high-affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy

AU - Weimar, Thomas

AU - Petersen, Bent O.

AU - Svensson, Birte

AU - Pinto, B. Mario

N1 - Funding Information: This work was supported with grants from the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industry (to T.W.), NATO (CRG #931165), and the Natural Sciences and Engineering Research Council of Canada. We are also grateful to K. Bock and M. Meldal for the gift of GAC. Copyright: Copyright 2007 Elsevier B.V., All rights reserved.

PY - 2000/5/19

Y1 - 2000/5/19

N2 - The determination of the bound solution conformation of D-gluco- dihydroacarbose (GAC), a tight-binding inhibitor of several glycosidase and amylase enzymes, by glucoamylase is described. Transferred NOE NMR experiments and line-broadening effects indicate that GAC is bound in a conformation resembling that observed in the crystal structure. This contrasts with the predominant conformation of GAC when free in solution. The NMR results also suggest regions on the carbohydrate that are in close contact with the protein. The determination of the bound solution conformation of GAC by glucoamylase using transferred NOE (trNOE) measurements is a significant achievement given the high affinity constant (K(a) = 3 x 107 M-1) for this receptor-ligand pair. It is striking that the off-rate for complexation is still sufficiently high to permit observation of trNOEs. (C) 2000 Elsevier Science Ltd.

AB - The determination of the bound solution conformation of D-gluco- dihydroacarbose (GAC), a tight-binding inhibitor of several glycosidase and amylase enzymes, by glucoamylase is described. Transferred NOE NMR experiments and line-broadening effects indicate that GAC is bound in a conformation resembling that observed in the crystal structure. This contrasts with the predominant conformation of GAC when free in solution. The NMR results also suggest regions on the carbohydrate that are in close contact with the protein. The determination of the bound solution conformation of GAC by glucoamylase using transferred NOE (trNOE) measurements is a significant achievement given the high affinity constant (K(a) = 3 x 107 M-1) for this receptor-ligand pair. It is striking that the off-rate for complexation is still sufficiently high to permit observation of trNOEs. (C) 2000 Elsevier Science Ltd.

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U2 - 10.1016/S0008-6215(00)00021-5

DO - 10.1016/S0008-6215(00)00021-5

M3 - Journal articles

C2 - 16001506

AN - SCOPUS:0034685673

SN - 0008-6215

VL - 326

SP - 50

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JO - Carbohydrate Research

JF - Carbohydrate Research

IS - 1

ER -

Determination of the solution conformation of D-gluco-dihydroacarbose, a high-affinity inhibitor bound to glucoamylase by transferred NOE NMR spectroscopy

Abstract

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