1CSS
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
Summary for 1CSS
| Entry DOI | 10.2210/pdb1css/pdb |
| Descriptor | CITRATE SYNTHASE, OXALOACETATE ION, ALPHA-FLUORO-CARBOXYMETHYLDETHIA COENZYME A COMPLEX, ... (4 entities in total) |
| Functional Keywords | oxo-acid-lyase |
| Biological source | Gallus gallus (chicken) |
| Cellular location | Mitochondrion matrix: P23007 |
| Total number of polymer chains | 1 |
| Total formula weight | 49117.49 |
| Authors | Usher, K.C.,Remington, S.J. (deposition date: 1995-08-04, release date: 1995-10-15, Last modification date: 2024-02-07) |
| Primary citation | 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 Cited by 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: 7492547DOI: 10.1021/bi00047a010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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