Acta Crystallographica Section D

Biological Crystallography

Volume 61, Part 11 (November 2005)

research papers

Acta Cryst. (2005). D61, 1508-1513 [ doi:10.1107/S0907444905026740 ]

Structural analysis of human liver glyceraldehyde-3-phosphate dehydrogenase

S. A. Ismail and H. W. Park

Abstract: The crystal structure of human liver glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been determined. This structure represents the first moderate-resolution (2.5 Å) and crystallographically refined (R_free = 22.9%) human GAPDH structure. The liver GAPDH structure consists of a homotetramer, each subunit of which is bound to a nicotinamide adenine dinucleotide (NAD⁺) molecule. The GAPDH enzyme has glycolytic and non-glycolytic functions, both of which are of chemotherapeutic interest. The availability of a high-quality human GAPDH structure is a necessity for structure-based drug design. In this study, structural differences between human liver and skeletal muscle GAPDHs are reported in order to understand how these two enzymes might respond to anti-trypanosomatid GAPDH inhibitors.

PDB reference: 1znq

Keywords: human glyceraldehyde-3-phosphate dehydrogenase; anti-trypanosomatid compounds; anti-apoptotic deprenyl.