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2zch

From Proteopedia

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Crystal structure of human prostate specific antigen complexed with an activating antibody

Structural highlights

2zch is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.83Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2zch"

@@ Line 3: / Line 3: @@
 <StructureSection load='2zch' size='340' side='right'caption='[[2zch]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2zch]] 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=2ZCH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ZCH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2zch]] 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=2ZCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZCH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.83&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zck|2zck]], [[2zcl|2zcl]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2zch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zch OCA], [https://pdbe.org/2zch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zch RCSB], [https://www.ebi.ac.uk/pdbsum/2zch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zch 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=2zch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zch OCA], [http://pdbe.org/2zch PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zch RCSB], [http://www.ebi.ac.uk/pdbsum/2zch PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zch ProSAT]</span></td></tr>
 </table>
 == 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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 40: / Line 39: @@
 [[Category: Large Structures]]
 [[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: Polymorphism]]
-[[Category: Prostate cancer]]
-[[Category: Protease]]
-[[Category: Secreted]]
-[[Category: Serine protease]]
-[[Category: Zymogen]]

2zch

From Proteopedia

Current revision

Crystal structure of human prostate specific antigen complexed with an activating antibody

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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