Conference paper

The High Resolution Structure of GDP-4-keto-6-deoxy-D-mannose epimerase/reductase

Camillo Rosano ; Department of Physics-INFM and Advanced Biotechnology Center-IST, University of Genova, Largo Rosanna Benzi, 10; I-16132 Genova, Italy
Gaetano Izzo ; Department of Physics-INFM and Advanced Biotechnology Center-IST, University of Genova, Largo Rosanna Benzi, 10; I-16132 Genova, Italy
Laura Sturla ; Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV; 1. I-16132 Genova, Italy
Angela Bisso ; Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV; 1. I-16132 Genova, Italy
Michela Tonetti ; Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV; 1. I-16132 Genova, Italy
Martino Bolognesi ; Department of Physics-INFM and Advanced Biotechnology Center-IST, University of Genova, Largo Rosanna Benzi, 10; I-16132 Genova, Italy

Abstract

GDP-4-keto-6-deoxy-D-mannose epimerase/reductase is a bifunctional enzyme involved in the biosynthesis of cell-surface structures, such as blood group antigens. Each subunit in the homodimeric enzyme consists of two domains. The N-terminal domain displays a Rossmann-fold topology and binds the NADP+ coenzyme. The C-terminal domain is held to bind the substrate. The holo-enzyme structure has been refined at 1.45 Å resolution, based on synchrotron data, to a final R-factor of 0.127 (R_free = 0.167). The refined protein model highlights several residues involved in coenzyme recognition and binding and suggests that the enzyme belongs to the short-chain dehydrogenase protein homology family. Implications of the catalytic mechanism are discussed.

Keywords

fucose metabolism; enzyme structure; short-chain dehydrogenase; NADP⁺; epimerization; cell surface antigens; high resolution protein crystallography

Hrčak ID:

132032

URI

https://hrcak.srce.hr/132032

Publication date:

4.9.2000.

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