|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1ekb' size='340' side='right'caption='[[1ekb]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1ekb' size='340' side='right'caption='[[1ekb]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ekb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EKB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ekb]] is a 3 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=1EKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EKB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=LYK:(2S)-2,6-DIAMINOHEXANE-1,1-DIOL'>LYK</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=LYK:(2S)-2,6-DIAMINOHEXANE-1,1-DIOL'>LYK</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Enteropeptidase Enteropeptidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.9 3.4.21.9] </span></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=1ekb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ekb OCA], [https://pdbe.org/1ekb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ekb RCSB], [https://www.ebi.ac.uk/pdbsum/1ekb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ekb ProSAT]</span></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=1ekb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ekb OCA], [https://pdbe.org/1ekb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ekb RCSB], [https://www.ebi.ac.uk/pdbsum/1ekb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ekb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ENTK_BOVIN ENTK_BOVIN]] Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.
| + | [https://www.uniprot.org/uniprot/ENTK_BOVIN ENTK_BOVIN] Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 34: |
Line 33: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Enteropeptidase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fuetterer, K]] | + | [[Category: Fuetterer K]] |
| - | [[Category: Lu, D]] | + | [[Category: Lu D]] |
| - | [[Category: Sadler, J E]] | + | [[Category: Sadler JE]] |
| - | [[Category: Waksman, G]] | + | [[Category: Waksman G]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Trypsinogen activation]]
| + | |
| Structural highlights
Function
ENTK_BOVIN Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Enteropeptidase is a membrane-bound serine protease that initiates the activation of pancreatic hydrolases by cleaving and activating trypsinogen. The enzyme is remarkably specific and cleaves after lysine residues of peptidyl substrates that resemble trypsinogen activation peptides such as Val-(Asp)4-Lys. To characterize the determinants of substrate specificity, we solved the crystal structure of the bovine enteropeptidase catalytic domain to 2.3 A resolution in complex with the inhibitor Val-(Asp)4-Lys-chloromethane. The catalytic mechanism and contacts with lysine at substrate position P1 are conserved with other trypsin-like serine proteases. However, the aspartyl residues at positions P2-P4 of the inhibitor interact with the enzyme surface mainly through salt bridges with the Nzeta atom of Lys99. Mutation of Lys99 to Ala, or acetylation with acetic anhydride, specifically prevented the cleavage of trypsinogen or Gly-(Asp)4-Lys-beta-naphthylamide and reduced the rate of inhibition by Val-(Asp)4-Lys-chloromethane 22 to 90-fold. For these reactions, Lys99 was calculated to account for 1.8 to 2.5 kcal mol(-1) of the free energy of transition state binding. Thus, a unique basic exosite on the enteropeptidase surface has evolved to facilitate the cleavage of its physiological substrate, trypsinogen.
Crystal structure of enteropeptidase light chain complexed with an analog of the trypsinogen activation peptide.,Lu D, Futterer K, Korolev S, Zheng X, Tan K, Waksman G, Sadler JE J Mol Biol. 1999 Sep 17;292(2):361-73. PMID:10493881[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lu D, Futterer K, Korolev S, Zheng X, Tan K, Waksman G, Sadler JE. Crystal structure of enteropeptidase light chain complexed with an analog of the trypsinogen activation peptide. J Mol Biol. 1999 Sep 17;292(2):361-73. PMID:10493881 doi:http://dx.doi.org/10.1006/jmbi.1999.3089
|
