1css: Difference between revisions

Revision as of 13:04, 2 May 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1CSS is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.

ReferenceReference

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., Schwartz B, Drueckhammer DG, Usher KC, Remington SJ, Biochemistry. 1995 Nov 28;34(47):15459-66. PMID:7492547 Page seeded by OCA on Fri May 2 13:04:46 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1css.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1css |SIZE=350|CAPTION= <scene name='initialview01'>1css</scene>, resolution 1.70&Aring;
+The line below this paragraph, containing "STRUCTURE_1css", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=FCX:ALPHA-FLUORO-CARBOXYMETHYLDETHIA+COENZYME+A+COMPLEX'>FCX</scene>, <scene name='pdbligand=OAA:OXALOACETATE+ION'>OAA</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Citrate_(Si)-synthase Citrate (Si)-synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.1 2.3.3.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1css|  PDB=1css  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1css FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1css OCA], [http://www.ebi.ac.uk/pdbsum/1css PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1css RCSB]</span>
-}}
 '''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'''
@@ Line 23: / Line 20: @@
 ==Reference==
 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., Schwartz B, Drueckhammer DG, Usher KC, Remington SJ, Biochemistry. 1995 Nov 28;34(47):15459-66. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7492547 7492547]
-[[Category: Citrate (Si)-synthase]]
 [[Category: Gallus gallus]]
 [[Category: Single protein]]
 [[Category: Remington, S J.]]
 [[Category: Usher, K C.]]
-[[Category: oxo-acid-lyase]]
+[[Category: Oxo-acid-lyase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 13:04:46 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:27:51 2008''