6t0p
From Proteopedia
(Difference between revisions)
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==Cationic Trypsin in Complex with a D-Phe-Pro-2-aminopyridine derivative== | ==Cationic Trypsin in Complex with a D-Phe-Pro-2-aminopyridine derivative== | ||
| - | <StructureSection load='6t0p' size='340' side='right'caption='[[6t0p]]' scene=''> | + | <StructureSection load='6t0p' size='340' side='right'caption='[[6t0p]], [[Resolution|resolution]] 1.19Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T0P OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6t0p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T0P FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.19Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=M6Q:(2~{S})-1-[(2~{R})-2-azanyl-3-phenyl-propanoyl]-~{N}-[(2-azanylpyridin-4-yl)methyl]pyrrolidine-2-carboxamide'>M6Q</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t0p OCA], [https://pdbe.org/6t0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t0p RCSB], [https://www.ebi.ac.uk/pdbsum/6t0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t0p ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:32011145</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6t0p" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Trypsin 3D structures|Trypsin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bos taurus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Heine A]] | [[Category: Heine A]] | ||
[[Category: Klebe G]] | [[Category: Klebe G]] | ||
[[Category: Ngo K]] | [[Category: Ngo K]] | ||
Revision as of 12:51, 24 January 2024
Cationic Trypsin in Complex with a D-Phe-Pro-2-aminopyridine derivative
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Categories: Bos taurus | Large Structures | Heine A | Klebe G | Ngo K
