6t5w | pdb_00006t5w

Cationic Trypsin in Complex with a D-Phe-Pro-p-aminopyridine Derivative (cocrystallizaton at 291 K)

spinqualitylabelsall models 6t5w, resolution 1.13Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.13Å Ligands: CA, DMS, J5K, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Trypsin and thrombin, structurally similar serine proteases, recognize different substrates; thrombin cleaves after Arg, whereas trypsin cleaves after Lys/Arg. Both recognize basic substrate headgroups via Asp189 at the bottom of the S1 pocket. By crystallography and isothermal titration calorimetry (ITC), we studied a series of d-Phe/d-DiPhe-Pro-(amino)pyridines. Identical ligand pairs show the same binding poses. Surprisingly, one ligand binds to trypsin in protonated state and to thrombin in unprotonated state at P1 along with differences in the residual solvation pattern. While trypsin binding is mediated by an ordered water molecule, in thrombin, water is scattered over three hydration sites. Although having highly similar S1 pockets, our results suggest different electrostatic properties of Asp189 possibly contributing to the selectivity determinant. Thrombin binds a specific Na(+) ion next to Asp189, which is absent in trypsin. The electrostatic properties across the S1 pocket are further attenuated by charged Glu192 at the rim of S1 in thrombin, which is replaced by uncharged Gln192 in trypsin. Protein-Induced Change in Ligand Protonation during Trypsin and Thrombin Binding: Hint on Differences in Selectivity Determinants of Both Proteins?,Ngo K, Collins-Kautz C, Gerstenecker S, Wagner B, Heine A, Klebe G J Med Chem. 2020 Mar 26;63(6):3274-3289. doi: 10.1021/acs.jmedchem.9b02061. Epub , 2020 Feb 24. PMID:32011145 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Trypsin 3D structures

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