5mnx: Difference between revisions
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==Neutron structure of cationic trypsin in complex with 2-aminopyridine== | |||
<StructureSection load='5mnx' size='340' side='right' caption='[[5mnx]], [[Resolution|resolution]] 1.42Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5mnx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MNX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MNX FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2AP:2-AMINOPYRIDINE'>2AP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mnx OCA], [http://pdbe.org/5mnx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mnx RCSB], [http://www.ebi.ac.uk/pdbsum/5mnx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mnx ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hydrogen atoms play a key role in protein-ligand recognition. They determine the quality of established H-bonding networks and define the protonation of bound ligands. Structural visualization of H atoms by X-ray crystallography is rarely possible. We used neutron diffraction to determine the positions of the hydrogen atoms in the ligands aniline and 2-aminopyridine bound to the archetypical serine protease trypsin. The resulting structures show the best resolution so far achieved for proteins larger than 100 residues and allow an accurate description of the protonation states and interactions with nearby water molecules. Despite its low pKa of 4.6 and a large distance of 3.6 A to the charged Asp189 at the bottom of the S1 pocket, the amino group of aniline becomes protonated, whereas in 2-aminopyridine, the pyridine nitrogen picks up the proton although its amino group is 1.6 A closer to Asp189. Therefore, apart from charge-charge distances, tautomer stability is decisive for the resulting binding poses, an aspect that is pivotal for predicting correct binding. | |||
Charges Shift Protonation: Neutron Diffraction Reveals that Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin.,Schiebel J, Gaspari R, Sandner A, Ngo K, Gerber HD, Cavalli A, Ostermann A, Heine A, Klebe G Angew Chem Int Ed Engl. 2017 Apr 18;56(17):4887-4890. doi:, 10.1002/anie.201701038. Epub 2017 Mar 28. PMID:28371253<ref>PMID:28371253</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5mnx" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Trypsin]] | |||
[[Category: Heine, A]] | |||
[[Category: Klebe, G]] | |||
[[Category: Ostermann, A]] | |||
[[Category: Schiebel, J]] | |||
[[Category: Schrader, T E]] | |||
[[Category: Hydrogen bonding]] | |||
[[Category: Hydrolase]] | |||
[[Category: Protein-ligand interaction]] | |||
[[Category: Protonation]] | |||
Revision as of 16:36, 24 May 2017
Neutron structure of cationic trypsin in complex with 2-aminopyridineNeutron structure of cationic trypsin in complex with 2-aminopyridine
Structural highlights
Publication Abstract from PubMedHydrogen atoms play a key role in protein-ligand recognition. They determine the quality of established H-bonding networks and define the protonation of bound ligands. Structural visualization of H atoms by X-ray crystallography is rarely possible. We used neutron diffraction to determine the positions of the hydrogen atoms in the ligands aniline and 2-aminopyridine bound to the archetypical serine protease trypsin. The resulting structures show the best resolution so far achieved for proteins larger than 100 residues and allow an accurate description of the protonation states and interactions with nearby water molecules. Despite its low pKa of 4.6 and a large distance of 3.6 A to the charged Asp189 at the bottom of the S1 pocket, the amino group of aniline becomes protonated, whereas in 2-aminopyridine, the pyridine nitrogen picks up the proton although its amino group is 1.6 A closer to Asp189. Therefore, apart from charge-charge distances, tautomer stability is decisive for the resulting binding poses, an aspect that is pivotal for predicting correct binding. Charges Shift Protonation: Neutron Diffraction Reveals that Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin.,Schiebel J, Gaspari R, Sandner A, Ngo K, Gerber HD, Cavalli A, Ostermann A, Heine A, Klebe G Angew Chem Int Ed Engl. 2017 Apr 18;56(17):4887-4890. doi:, 10.1002/anie.201701038. Epub 2017 Mar 28. PMID:28371253[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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