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Structure and mechanism of soluble quinoprotein glucose dehydrogenase
Author(s) -
Oubrie Arthur,
Rozeboom Henriétte J.,
Kalk Kor H.,
Olsthoorn Arjen J.J.,
Duine Johannis A.,
Dijkstra Bauke W.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.19.5187
Subject(s) - library science , computer science
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 Å resolution, and of a complex with reduced PQQ and glucose at 1.9 Å 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.