1tx8 | pdb_00001tx8
| |||||||||||||
| 1tx8, resolution 1.7Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | CA and AM4 | ||||||||||||
| Activity: | Trypsin, with EC number 3.4.21.4 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Bovine Trypsin complexed with AMSO
Overview
We have designed, synthesized, and evaluated the factor Xa inhibitory activities of p-amidinophenyl-sulfones, amines, and alcohols intended to take advantage of the polarity and hydrogen-bonding potential of the oxyanion hole region of the S1 specificity pocket. We demonstrate that placement of an anionic group within the oxyanion hole region of the catalytic site substantially enhances activity, with small flexible groups favored over bulkier ones. Ab initio pKa calculations suggest that the hydroxyl substituent frequently used for benzamidine moieties may be ionized to form an anionic group, consistent with the general trend. One nonamidine based substituent also shows promising activity.
About this Structure
1TX8 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Design, synthesis, and evaluation of oxyanion-hole selective inhibitor substituents for the S1 subsite of factor Xa., Rumthao S, Lee O, Sheng Q, Fu W, Mulhearn DC, Crich D, Mesecar AD, Johnson ME, Bioorg Med Chem Lett. 2004 Oct 18;14(20):5165-70. PMID:15380220
Page seeded by OCA on Thu Mar 20 14:24:26 2008
