4R7P

Human UDP-glucose pyrophosphorylase isoform 1 in complex with UDP-glucose

Summary for 4R7P

• Entry DOI: 10.2210/pdb4r7p/pdb
• Related: 3R2W 3R3I
• Descriptor: UTP--glucose-1-phosphate uridylyltransferase, URIDINE-5'-DIPHOSPHATE-GLUCOSE, SULFATE ION, ... (7 entities in total)
• Functional Keywords: rossmann-like alpha/beta/alpha sandwich fold, pyrophosphorylase, utp, glc-1-p, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q16851
• Total number of polymer chains: 4
• Total formula weight: 239454.47

Authors

Fuehring, J.,Cramer, J.T.,Schneider, J.,Baruch, P.,Gerardy-Schahn, R.,Fedorov, R. (deposition date: 2014-08-28, release date: 2015-04-22, Last modification date: 2024-02-28)

Primary citation

Fuhring, J.I.,Cramer, J.T.,Schneider, J.,Baruch, P.,Gerardy-Schahn, R.,Fedorov, R.
A Quaternary Mechanism Enables the Complex Biological Functions of Octameric Human UDP-glucose Pyrophosphorylase, a Key Enzyme in Cell Metabolism.
Sci Rep, 5:9618-9618,

PubMed Abstract: In mammals, UDP-glucose pyrophosphorylase (UGP) is the only enzyme capable of activating glucose-1-phosphate (Glc-1-P) to UDP-glucose (UDP-Glc), a metabolite located at the intersection of virtually all metabolic pathways in the mammalian cell. Despite the essential role of its product, the molecular basis of UGP function is poorly understood. Here we report the crystal structure of human UGP in complex with its product UDP-Glc. Beyond providing first insight into the active site architecture, we describe the substrate binding mode and intermolecular interactions in the octameric enzyme that are crucial to its activity. Importantly, the quaternary mechanism identified for human UGP in this study may be common for oligomeric sugar-activating nucleotidyltransferases. Elucidating such mechanisms is essential for understanding nucleotide sugar metabolism and opens the perspective for the development of drugs that specifically inhibit simpler organized nucleotidyltransferases in pathogens.

PubMed: 25860585
DOI: 10.1038/srep09618

Experimental method

X-RAY DIFFRACTION (3.35 Å)