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| | <StructureSection load='2zcl' size='340' side='right'caption='[[2zcl]], [[Resolution|resolution]] 3.25Å' scene=''> | | <StructureSection load='2zcl' size='340' side='right'caption='[[2zcl]], [[Resolution|resolution]] 3.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zcl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZCL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ZCL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zcl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZCL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZCL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3.25Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zch|2zch]], [[2zck|2zck]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Semenogelase Semenogelase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.77 3.4.21.77] </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=2zcl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zcl OCA], [https://pdbe.org/2zcl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zcl RCSB], [https://www.ebi.ac.uk/pdbsum/2zcl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zcl ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2zcl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zcl OCA], [http://pdbe.org/2zcl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zcl RCSB], [http://www.ebi.ac.uk/pdbsum/2zcl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zcl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KLK3_HUMAN KLK3_HUMAN]] Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum. | + | [https://www.uniprot.org/uniprot/KLK3_HUMAN KLK3_HUMAN] Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Semenogelase]]
| + | [[Category: Jolivet-Reynaud C]] |
| - | [[Category: Jolivet-Reynaud, C]] | + | [[Category: Menez R]] |
| - | [[Category: Menez, R]] | + | [[Category: Stura E]] |
| - | [[Category: Stura, E]] | + | |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Human psa]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Kallikrein related peptidase]]
| + | |
| - | [[Category: Prostate cancer]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
KLK3_HUMAN Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.
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
Human prostate-specific antigen (PSA or KLK3) is an important marker for the diagnosis and management of prostate cancer. This is an androgen-regulated glycoprotein of the kallikrein-related protease family secreted by prostatic epithelial cells. Its physiological function is to cleave semenogelins in the seminal coagulum and its enzymatic activity is strongly modulated by zinc ions. Here we present the first crystal structure of human PSA in complex with monoclonal antibody (mAb) 8G8F5 that enhances its enzymatic activity. The mAb recognizes an epitope composed of five discontinuous segments including residues from the kallikrein loop and stabilizes PSA in an "open and active conformation" that accelerates catalysis. We also present the crystal structure of PSA in complex with both the mAb 8G8F5 and a fluorogenic substrate Mu-KGISSQY-AFC, derived from semenogelin I. By exploiting the inhibition of PSA by zinc ions, we were able to obtain a substrate acyl intermediate covalently linked to the catalytic serine, at pH 7.3 but not at pH 5.5. Moreover, the inhibition of PSA activity by zinc was found to be modulated by pH variations but not by the antibody binding. The correlation of the different data with the physiological conditions under which PSA can cleave semenogelins is discussed.
Crystal structure of a ternary complex between human prostate-specific antigen, its substrate acyl intermediate and an activating antibody.,Menez R, Michel S, Muller BH, Bossus M, Ducancel F, Jolivet-Reynaud C, Stura EA J Mol Biol. 2008 Feb 29;376(4):1021-33. Epub 2007 Nov 22. PMID:18187150[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Menez R, Michel S, Muller BH, Bossus M, Ducancel F, Jolivet-Reynaud C, Stura EA. Crystal structure of a ternary complex between human prostate-specific antigen, its substrate acyl intermediate and an activating antibody. J Mol Biol. 2008 Feb 29;376(4):1021-33. Epub 2007 Nov 22. PMID:18187150 doi:http://dx.doi.org/10.1016/j.jmb.2007.11.052
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