1TX8

Bovine Trypsin complexed with AMSO

Summary for 1TX8

• Entry DOI: 10.2210/pdb1tx8/pdb
• Related: 1TX7
• Descriptor: Trypsinogen, CALCIUM ION, 4-(METHYLSULFONYL)BENZENECARBOXIMIDAMIDE, ... (4 entities in total)
• Functional Keywords: trypsin, hydrolase
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 23562.61

Authors

Mesecar, A.D. (deposition date: 2004-07-02, release date: 2005-10-18, Last modification date: 2024-11-20)

Primary citation

Rumthao, S.,Lee, O.,Sheng, Q.,Fu, W.,Mulhearn, D.C.,Crich, D.,Mesecar, A.D.,Johnson, M.E.
Design, synthesis, and evaluation of oxyanion-hole selective inhibitor substituents for the S1 subsite of factor Xa
Bioorg.Med.Chem.Lett., 14:5165-5170, 2004

PubMed Abstract: 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.

PubMed: 15380220
DOI: 10.1016/j.bmcl.2004.07.054

Experimental method

X-RAY DIFFRACTION (1.7 Å)