2VT5

FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE -1- PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH A DUAL BINDING AMP SITE INHIBITOR

Summary for 2VT5

• Entry DOI: 10.2210/pdb2vt5/pdb
• Related: 1FTA 2FHY 2FIE 2FIX 2JJK
• Descriptor: FRUCTOSE-1,6-BISPHOSPHATASE 1, 4-AMINO-N-[(2-SULFANYLETHYL)CARBAMOYL]BENZENESULFONAMIDE (3 entities in total)
• Functional Keywords: hydrolase (phosphoric monoester), disease mutation, allosteric enzyme, zinc, hydrolase, polymorphism, gluconeogenesis, carbohydrate metabolism
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 8
• Total formula weight: 297078.13

Authors

Ruf, A.,Joseph, C.,Benz, J.,Fol, B.,Tetaz, T. (deposition date: 2008-05-09, release date: 2008-07-22, Last modification date: 2024-05-08)

Primary citation

Hebeisen, P.,Kuhn, B.,Kohler, P.,Gubler, M.,Huber, W.,Kitas, E.,Schott, B.,Benz, J.,Joseph, C.,Ruf, A.
Allosteric Fbpase Inhibitors Gain 10(5) Times in Potency When Simultaneously Binding Two Neighboring AMP Sites.
Bioorg.Med.Chem.Lett., 18:4708-, 2008

PubMed Abstract: Human fructose-1,6-bisphosphatase (FBPase, EC 3.1.3.11) is a key gluconeogenic enzyme, responsible for the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate, and thus presents an opportunity for the development of novel therapeutics focused on lowering the hepatic glucose production in type 2 diabetics. In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. In an HTS campaign aromatic sulfonylureas have been identified as FBPase inhibitors mimicking AMP. By bridging two adjacent allosteric binding sites using two aromatic sulfonylureas as anchor units and covalently linking them, it was possible to obtain dual binding AMP site inhibitors that exhibit a strong inhibitory effect.

PubMed: 18650089
DOI: 10.1016/J.BMCL.2008.06.103

Experimental method

X-RAY DIFFRACTION (2.2 Å)