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| | ==Human Kallikrein 4 complex with cobalt and p-aminobenzamidine== | | ==Human Kallikrein 4 complex with cobalt and p-aminobenzamidine== |
| - | <StructureSection load='2bdi' size='340' side='right' caption='[[2bdi]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='2bdi' size='340' side='right'caption='[[2bdi]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bdi]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BDI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bdi]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BDI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=PBZ:P-AMINO+BENZAMIDINE'>PBZ</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]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLK4, EMSP1, PRSS17, PSTS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=PBZ:P-AMINO+BENZAMIDINE'>PBZ</scene></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=2bdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bdi OCA], [http://pdbe.org/2bdi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bdi RCSB], [http://www.ebi.ac.uk/pdbsum/2bdi PDBsum]</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=2bdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bdi OCA], [https://pdbe.org/2bdi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bdi RCSB], [https://www.ebi.ac.uk/pdbsum/2bdi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bdi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:[http://omim.org/entry/204700 204700]]. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.<ref>PMID:15235027</ref> | + | [https://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN] Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:[https://omim.org/entry/204700 204700]. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.<ref>PMID:15235027</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Involved in enamel formation.<ref>PMID:15235027</ref> | + | [https://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN] Involved in enamel formation.<ref>PMID:15235027</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bd/2bdi_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bd/2bdi_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Kallikrein|Kallikrein]] | + | *[[Kallikrein 3D structures|Kallikrein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bode, W]] | + | [[Category: Large Structures]] |
| - | [[Category: Debela, M]] | + | [[Category: Bode W]] |
| - | [[Category: Goettig, P]] | + | [[Category: Debela M]] |
| - | [[Category: SPINE, Structural Proteomics in Europe]] | + | [[Category: Goettig P]] |
| - | [[Category: 70-80 loop]]
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| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: S1 subsite]]
| + | |
| - | [[Category: Serine proteinase]]
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| - | [[Category: Spine]]
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| - | [[Category: Structural genomic]]
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| - | [[Category: Structural proteomics in europe]]
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| Structural highlights
Disease
KLK4_HUMAN Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:204700. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.[1]
Function
KLK4_HUMAN Involved in enamel formation.[2]
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 tissue kallikrein 4 (hK4) belongs to a 15-member family of closely related serine proteinases. hK4 is predominantly expressed in prostate, activates hK3/PSA, and is up-regulated in prostate and ovarian cancer. We have identified active monomers of recombinant hK4 besides inactive oligomers in solution. hK4 crystallised in the presence of zinc, nickel, and cobalt ions in three crystal forms containing cyclic tetramers and octamers. These structures display a novel metal site between His25 and Glu77 that links the 70-80 loop with the N-terminal segment. Micromolar zinc as present in prostatic fluid inhibits the enzymatic activity of hK4 against fluorogenic substrates. In our measurements, wild-type hK4 exhibited a zinc inhibition constant (IC50) of 16 microM including a permanent residual activity, in contrast to the zinc-independent mutants H25A and E77A. Since the Ile16 N terminus of wild-type hK4 becomes more accessible for acetylating agents in the presence of zinc, we propose that zinc affects the hK4 active site via the salt-bridge formed between the N terminus and Asp194 required for a functional active site. hK4 possesses an unusual 99-loop that creates a groove-like acidic S2 subsite. These findings explain the observed specificity of hK4 for the P1 to P4 substrate residues. Moreover, hK4 shows a negatively charged surface patch, which may represent an exosite for prime-side substrate recognition.
Crystal structures of human tissue kallikrein 4: activity modulation by a specific zinc binding site.,Debela M, Magdolen V, Grimminger V, Sommerhoff C, Messerschmidt A, Huber R, Friedrich R, Bode W, Goettig P J Mol Biol. 2006 Oct 6;362(5):1094-107. Epub 2006 Aug 3. PMID:16950394[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hart PS, Hart TC, Michalec MD, Ryu OH, Simmons D, Hong S, Wright JT. Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J Med Genet. 2004 Jul;41(7):545-9. PMID:15235027
- ↑ Hart PS, Hart TC, Michalec MD, Ryu OH, Simmons D, Hong S, Wright JT. Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J Med Genet. 2004 Jul;41(7):545-9. PMID:15235027
- ↑ Debela M, Magdolen V, Grimminger V, Sommerhoff C, Messerschmidt A, Huber R, Friedrich R, Bode W, Goettig P. Crystal structures of human tissue kallikrein 4: activity modulation by a specific zinc binding site. J Mol Biol. 2006 Oct 6;362(5):1094-107. Epub 2006 Aug 3. PMID:16950394 doi:10.1016/j.jmb.2006.08.003
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