1CSR

Alpha-fluoro acid and alpha-fluoro amide analogs of acetyl-coa as inhibitors of of citrate synthase: effect of pka matching on binding affinity and hydrogen bond length

1CSR の概要

• エントリーDOI: 10.2210/pdb1csr/pdb
• 分子名称: CITRATE SYNTHASE, OXALOACETATE ION, ALPHA-FLUORO-AMIDOCARBOXYMETHYLDETHIA COENZYME A COMPLEX, ... (4 entities in total)
• 機能のキーワード: oxo-acid-lyase
• 由来する生物種: Gallus gallus (chicken)
• 細胞内の位置: Mitochondrion matrix: P23007
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49116.51

構造登録者

Usher, K.C.,Remington, S.J. (登録日: 1995-08-04, 公開日: 1995-10-15, 最終更新日: 2024-02-07)

主引用文献

Schwartz, B.,Drueckhammer, D.G.,Usher, K.C.,Remington, S.J.
alpha-Fluoro acid and alpha-fluoro amide analogs of acetyl-CoA as inhibitors of citrate synthase: effect of pKa matching on binding affinity and hydrogen bond length.
Biochemistry, 34:15459-15466, 1995

PubMed Abstract: An alpha-fluoro acid analog and an alpha-fluoro amide analog of acetyl-CoA have been synthesized. The ternary complexes of these inhibitors with oxaloacetate and citrate synthase have been crystallized and their structures analyzed at 1.7 A resolution. The structures are similar to those reported for the corresponding non-fluorinated analogs (Usher et al., 1994), with all forming unusually short hydrogen bonds to Asp 375. The alpha-fluoro amide analog binds with an affinity 1.5-fold lower than that of a previously described amide analog lacking the alpha-fluoro group. The alpha-fluoro acid analog binds with a 50-fold decreased affinity relative to the corresponding unfluorinated analog. The binding affinities are consistent with increased strengths of hydrogen bonds to Asp 375 with closer matching of pKa values between hydrogen bond donors and acceptors. The results do not support any direct correlation between hydrogen bond strength and hydrogen bond length in enzyme-inhibitor complexes.

PubMed: 7492547
DOI: 10.1021/bi00047a010

実験手法

X-RAY DIFFRACTION (1.7 Å)