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

2VT5 の概要

• エントリーDOI: 10.2210/pdb2vt5/pdb
• 関連するPDBエントリー: 1FTA 2FHY 2FIE 2FIX 2JJK
• 分子名称: FRUCTOSE-1,6-BISPHOSPHATASE 1, 4-AMINO-N-[(2-SULFANYLETHYL)CARBAMOYL]BENZENESULFONAMIDE (3 entities in total)
• 機能のキーワード: hydrolase (phosphoric monoester), disease mutation, allosteric enzyme, zinc, hydrolase, polymorphism, gluconeogenesis, carbohydrate metabolism
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 297078.13

構造登録者

Ruf, A.,Joseph, C.,Benz, J.,Fol, B.,Tetaz, T. (登録日: 2008-05-09, 公開日: 2008-07-22, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)