3PM3: Bovine Trypsin Variant X(tripleile227) In Complex With Small Molecule Inhibitor

Citation:
Abstract
A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine proteinase inhibitors with trypsin variants onto which the ligand-binding site of factor Xa has been grafted. Despite conservative mutations of only two residues not immediately in contact with ligands (second shell residues), significant differences in the affinity profiles of the variants are observed. Structural analyses demonstrate that these are due to multiple effects, including differences in the structure of the binding site, differences in target flexibility and differences in inhibitor binding modes. The data presented here highlight the myriad competing microscopic processes that contribute to protein-ligand interactions and emphasize the difficulties in predicting affinity from structure.
PDB ID: 3PM3Download
MMDB ID: 95503
PDB Deposition Date: 2010/11/16
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 1.53  Å
Source Organism:
Similar Structures:
Biological Unit for 3PM3: monomeric; determined by author
Molecular Components in 3PM3
Label Count Molecule
Protein (1 molecule)
1
Cationic Trypsin(Gene symbol: PRSS1)
Molecule annotation
Chemicals (7 molecules)
1
1
2
1
3
3
4
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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