Thermodynamic Signature of Substrates and Substrate Analogs Binding to Human Blood Group B Galactosyltransferase from Isothermal Titration Calorimetry Experiments

Biopolymers ◽  
2013 ◽  
Vol 99 (10) ◽  
pp. 784-795 ◽  
Author(s):  
Nora Sindhuwinata ◽  
Lena L. Grimm ◽  
Sophie Weißbach ◽  
Sabrina Zinn ◽  
Eva Munoz ◽  
...  
Keyword(s):  
Blood Group ◽  
Isothermal Titration Calorimetry ◽  
Human Blood ◽  
Titration Calorimetry ◽  
Substrate Analogs ◽  
Human Blood Group ◽  
Group B

scholarly journals Fragment-based Screening of the Donor Substrate Specificity of Human Blood Group B Galactosyltransferase Using Saturation Transfer Difference NMR

2006 ◽  
Vol 281 (43) ◽  
pp. 32728-32740 ◽  
Author(s):  
Astrid Blume ◽  
Jesus Angulo ◽  
Thorsten Biet ◽  
Hannelore Peters ◽  
Andrew J. Benie ◽  
...  
Keyword(s):  
Blood Group ◽  
Human Blood ◽  
Specific Binding ◽  
Binding Pocket ◽  
Saturation Transfer ◽  
Substrate Analogs ◽  
Human Blood Group ◽  
Donor Substrate ◽  
Saturation Transfer Difference ◽  
Group B

Saturation transfer difference NMR experiments on human blood group B α-(1,3)-galactosyltransferase (GTB) for the first time provide a comprehensive set of binding epitopes of donor substrate analogs in relation to the natural donor UDP-Gal. This study revealed that the enzyme binds several UDP-activated sugars, including UDP-Glc, UDP-GlcNAc, and UDP-GalNAc. In all cases, UDP is the dominant binding epitope. To identify the minimum requirements for specific binding, a detailed analysis utilizing a fragment-based approach was employed. The binding of donor substrate to GTB is essentially controlled by the base as a “molecular anchor.” Uracil represents the smallest fragment that is recognized, whereas CDP, AMP, and GDP do not exhibit any significant binding affinity for the enzyme. The ribose and β-phosphate moieties increase the affinity of the ligands, whereas the pyranose sugar apparently weakens the binding, although this part of the molecule controls the specificity of the enzyme. Accordingly, UDP represents the best binder. The binding affinities of UDP-Gal, UDP-Glc, and UMP are about the same, but lower than that of UDP. Furthermore, we observed that β-d-galactose and α-d-galactose bind weakly to GTB. Whereas β-d-galactose binds to the acceptor and donor sites, it is suggested that α-d-galactose occupies a third hitherto unknown binding pocket. Finally, our experiments revealed that modulation of enzymatic activity by metal ions critically depends on the total enzyme concentration, raising the question as to which of the bivalent metal cations Mg2+ and Mn2+ is more relevant under physiological conditions.

scholarly journals A Single Point Mutation Reverses the Donor Specificity of Human Blood Group B-synthesizing Galactosyltransferase

2003 ◽  
Vol 278 (14) ◽  
pp. 12403-12405 ◽  
Author(s):  
Sandra L. Marcus ◽  
Robert Polakowski ◽  
Nina O. L. Seto ◽  
Eeva Leinala ◽  
Svetlana Borisova ◽  
...  
Keyword(s):  
Point Mutation ◽  
Blood Group ◽  
Human Blood ◽  
Single Point ◽  
Single Point Mutation ◽  
Human Blood Group ◽  
Group B

scholarly journals Structural Effects of Naturally Occurring Human Blood Group B Galactosyltransferase Mutations Adjacent to the DXD Motif

2007 ◽  
Vol 282 (13) ◽  
pp. 9564-9570 ◽  
Author(s):  
Mattias Persson ◽  
James A. Letts ◽  
Bahram Hosseini-Maaf ◽  
Svetlana N. Borisova ◽  
Monica M. Palcic ◽  
...  
Keyword(s):  
Blood Group ◽  
Human Blood ◽  
Structural Effects ◽  
Human Blood Group ◽  
Naturally Occurring ◽  
Group B

NMR-based exploration of the acceptor binding site of human blood group B galactosyltransferase with molecular fragments

2010 ◽  
Vol 27 (3) ◽  
pp. 349-358 ◽  
Author(s):  
Christoph Rademacher ◽  
Jens Landström ◽  
Nora Sindhuwinata ◽  
Monica M. Palcic ◽  
Göran Widmalm ◽  
...  
Keyword(s):  
Binding Site ◽  
Blood Group ◽  
Human Blood ◽  
Molecular Fragments ◽  
Human Blood Group ◽  
Group B

Human blood group B-active ganglio-glycosphingolipid in rat glioma

1993 ◽  
Vol 1170 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Suetake Keiji ◽  
Gasa Shinsei ◽  
Taki Takao ◽  
Chiba Masahiko ◽  
Yamaki Toshiaki ◽  
...  
Keyword(s):  
Blood Group ◽  
Human Blood ◽  
Rat Glioma ◽  
Human Blood Group ◽  
Group B

Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase

Transfusion ◽  
2007 ◽  
Vol 47 (5) ◽  
pp. 864-875 ◽  
Author(s):  
Bahram Hosseini-Maaf ◽  
James A. Letts ◽  
Mattias Persson ◽  
Elizabeth Smart ◽  
Pierre-Yves LePennec ◽  
...  
Keyword(s):  
Blood Group ◽  
Human Blood ◽  
Structural Basis ◽  
Red Cell ◽  
Phenotypic Changes ◽  
Human Blood Group ◽  
Naturally Occurring ◽  
Group B
Sign in / Sign up

Export Citation Format

Share Document