Publication Date:
2011-10-11
Description:
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). 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-A 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 form 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fushinobu, Shinya -- Nishimasu, Hiroshi -- Hattori, Daiki -- Song, Hyun-Jin -- Wakagi, Takayoshi -- England -- Nature. 2011 Oct 9;478(7370):538-41. doi: 10.1038/nature10457.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21983966" target="_blank"〉PubMed〈/a〉
Keywords:
Biocatalysis
;
Catalytic Domain
;
Crystallography, X-Ray
;
Dihydroxyacetone Phosphate/metabolism
;
Fructose-Bisphosphate Aldolase/*chemistry/*metabolism
;
Fructosediphosphates/metabolism
;
Gluconeogenesis
;
Glyceraldehyde 3-Phosphate/metabolism
;
Lysine/metabolism
;
Magnesium/metabolism
;
Models, Molecular
;
Phosphoric Monoester Hydrolases/*chemistry/*metabolism
;
Phosphorylation
;
Protein Conformation
;
Schiff Bases/chemistry/metabolism
;
Sulfolobus/*enzymology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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