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| | <StructureSection load='1hia' size='340' side='right'caption='[[1hia]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1hia' size='340' side='right'caption='[[1hia]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1hia]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirme Hirme] and [https://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HIA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HIA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1hia]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HIA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HIA FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Tissue_kallikrein Tissue kallikrein], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.35 3.4.21.35] </span></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]] 2.4Å</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=1hia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hia OCA], [https://pdbe.org/1hia PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hia RCSB], [https://www.ebi.ac.uk/pdbsum/1hia PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hia 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=1hia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hia OCA], [https://pdbe.org/1hia PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hia RCSB], [https://www.ebi.ac.uk/pdbsum/1hia PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hia ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/KLK_PIG KLK_PIG]] Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. [[https://www.uniprot.org/uniprot/ANTA_HIRME ANTA_HIRME]] Acts as an inhibitor of tissue kallikrein, trypsin, chymotrypsin and neutrophil cathepsin G.
| + | [https://www.uniprot.org/uniprot/KLK_PIG KLK_PIG] Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hirme]] | + | [[Category: Hirudo medicinalis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pig]] | + | [[Category: Sus scrofa]] |
| - | [[Category: Tissue kallikrein]] | + | [[Category: Di Marco S]] |
| - | [[Category: Gruetter, M]] | + | [[Category: Gruetter M]] |
| - | [[Category: Marco, S Di]]
| + | [[Category: Mittl P]] |
| - | [[Category: Mittl, P]] | + | |
| - | [[Category: Kinin]]
| + | |
| - | [[Category: Psa]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Serpin]]
| + | |
| - | [[Category: Trypsin]]
| + | |
| Structural highlights
Function
KLK_PIG Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
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
BACKGROUND: Hirustasin belongs to a class of serine protease inhibitors characterized by a well conserved pattern of cysteine residues. Unlike the closely related inhibitors, antistasin/ghilanten and guamerin, which are selective for coagulation factor Xa or neutrophil elastase, hirustasin binds specifically to tissue kallikrein. The conservation of the pattern of cysteine residues and the significant sequence homology suggest that these related inhibitors possess a similar three-dimensional structure to hirustasin. RESULTS: The crystal structure of the complex between tissue kallikrein and hirustasin was analyzed at 2.4 resolution. Hirustasin folds into a brick-like structure that is dominated by five disulfide bridges and is sparse in secondary structural elements. The cysteine residues are connected in an abab cdecde pattern that causes the polypeptide chain to fold into two similar motifs. As a hydrophobic core is absent from hirustasin the disulfide bridges maintain the tertiary structure and present the primary binding loop to the active site of the protease. The general structural topography and disulfide connectivity of hirustasin has not previously been described. CONCLUSIONS: The crystal structure of the kallikrein-hirustasin complex reveals that hirustasin differs from other serine protease inhibitors in its conformation and its disulfide bond connectivity, making it the prototype for a new class of inhibitor. The disulfide pattern shows that the structure consists of two domains, but only the C-terminal domain interacts with the protease. The disulfide pattern of the N-terminal domain is related to the pattern found in other proteins. Kallikrein recognizes hirustasin by the formation of an antiparallel beta sheet between the protease and the inhibitor. The P1 arginine binds in a deep negatively charged pocket of the enzyme. An additional pocket at the periphery of the active site accommodates the sidechain of the P4 valine.
A new structural class of serine protease inhibitors revealed by the structure of the hirustasin-kallikrein complex.,Mittl PR, Di Marco S, Fendrich G, Pohlig G, Heim J, Sommerhoff C, Fritz H, Priestle JP, Grutter MG Structure. 1997 Feb 15;5(2):253-64. PMID:9032072[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mittl PR, Di Marco S, Fendrich G, Pohlig G, Heim J, Sommerhoff C, Fritz H, Priestle JP, Grutter MG. A new structural class of serine protease inhibitors revealed by the structure of the hirustasin-kallikrein complex. Structure. 1997 Feb 15;5(2):253-64. PMID:9032072
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