Structural basis for the bifunctionality of fructose-1,6-bisphosphate aldolase / phosphatase
In: Nature (London), Jg. 478 (2011), Heft 7370, S. 538-541
Online
academicJournal
- print, 12 ref
Zugriff:
Enzymes catalyse specific reactions and are essential for maintaining life. Although some are referred to as being bifunctional, they consist of either two distinct catalytic domains or a single domain that displays promiscuous substrate specificity'. Thus, one enzyme active site is generally responsible for one biochemical reaction. In contrast to this conventional concept, archaeal fructose-1,6-bisphosphate (FBP) aldolase/phosphatase (FBPA/P) consists of a single catalytic domain, but catalyses two chemically distinct reactions of gluconeogenesis: (1) the reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GA3P) to FBP; (2) the dephosphorylation of FBP to fructose-6-phosphate (F6P)2. Thus, FBPA/P is fundamentally different from ordinary enzymes whose active sites are responsible for a specific reaction. However, the molecular mechanism by which FBPA/P achieves its unusual bifunctionality remains unknown. Here we report the crystal structure of FBPA/P at 1.5-Å resolution in the aldolase form, where a critical lysine residue forms a Schiff base with DHAP. A structural comparison of the aldolase form with a previously determined phosphatase form3 revealed a dramatic conformational change in the active site, demonstrating that FBPA/P metamorphoses its active-site architecture to exhibit dual activities. Thus, our findings expand the conventional concept that one enzyme catalyses one biochemical reaction.
Titel: |
Structural basis for the bifunctionality of fructose-1,6-bisphosphate aldolase / phosphatase
|
---|---|
Autor/in / Beteiligte Person: | FUSHINOBU, Shinya ; NISHIMASU, Hiroshi ; HATTORI, Daiki ; SONG, Hyun-Jin ; WAKAGI, Takayoshi |
Link: | |
Zeitschrift: | Nature (London), Jg. 478 (2011), Heft 7370, S. 538-541 |
Veröffentlichung: | London: Nature Publishing Group, 2011 |
Medientyp: | academicJournal |
Umfang: | print, 12 ref |
ISSN: | 0028-0836 (print) |
Schlagwort: |
|
Sonstiges: |
|