US EPA

1178025 

Journal Article 

Structure and mechanism of soluble quinoprotein glucose dehydrogenase 

Oubrie, A; Rozeboom, HJ; Kalk, KH; Olsthoorn, AJJ; Duine, JA; Dijkstra, BW 

1999 

Yes 

EMBO Journal
ISSN: 0261-4189
EISSN: 1460-2075 

18 

19 

5187-5194 

English 

10508152 

10.1093/emboj/18.19.5187 

WOS:000083140800004 

Soluble glucose dehydrogenase (s-GDH; EC 1.1.99.17) is a classical quinoprotein which requires the cofactor pyrroloquinoline quinone (PQQ) to oxidize glucose to gluconolactone. The reaction mechanism of PQQ-dependent enzymes has remained controversial due to the absence of comprehensive structural data. We have determined the X-ray structure of s-GDH with the cofactor at 2.2 A resolution, and of a complex with reduced PQQ and glucose at 1.9 A resolution. These structures reveal the active site of s-GDH, and show for the first time how a functionally bound substrate interacts with the cofactor in a PQQ-dependent enzyme. Twenty years after the discovery of PQQ, our results finally provide conclusive evidence for a reaction mechanism comprising general base-catalyzed hydride transfer, rather than the generally accepted covalent addition-elimination mechanism. Thus, PQQ-dependent enzymes use a mechanism similar to that of nicotinamide- and flavin-dependent oxidoreductases. 

glucose dehydrogenase; hydride transfer; PQQ; reaction mechanism; X-ray structure