Structural analysis of human liver glyceraldehyde-3-phosphate dehydrogenase.
The crystal structure of human liver glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been determined. This structure represents the first moderate-resolution (2.5 A) and crystallographically refined (Rfree = 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.
Ismail
S A
SA
Department of Molecular Sciences, University of Tennessee Health Science Center, USA.
Park
H W
HW
D000818:Animals; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000201:enzymology; D010300:Parkinson Disease / Q000188:drug therapy; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014345:Trypanosoma / Q000201:enzymology; D014352:Trypanosomiasis / Q000188:drug therapy
D004791:Enzyme Inhibitors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases