4ecb

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<StructureSection load='4ecb' size='340' side='right'caption='[[4ecb]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='4ecb' size='340' side='right'caption='[[4ecb]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4ecb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ECB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ECB FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4ecb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Schistosoma_japonicum Schistosoma japonicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ECB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ECB FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ecc|4ecc]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ecb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ecb OCA], [https://pdbe.org/4ecb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ecb RCSB], [https://www.ebi.ac.uk/pdbsum/4ecb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ecb ProSAT]</span></td></tr>
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<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=4ecb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ecb OCA], [http://pdbe.org/4ecb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ecb RCSB], [http://www.ebi.ac.uk/pdbsum/4ecb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ecb ProSAT]</span></td></tr>
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</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/KNG1_HUMAN KNG1_HUMAN] Congenital high-molecular-weight kininogen deficiency. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/GST26_SCHJA GST26_SCHJA]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. GST isoenzymes appear to play a central role in the parasite detoxification system. Other functions are also suspected including a role in increasing the solubility of haematin in the parasite gut.
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[https://www.uniprot.org/uniprot/KNG1_HUMAN KNG1_HUMAN] (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting.[https://www.uniprot.org/uniprot/GST26_SCHJA GST26_SCHJA] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. GST isoenzymes appear to play a central role in the parasite detoxification system. Other functions are also suspected including a role in increasing the solubility of haematin in the parasite gut.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The study of synthetic peptides corresponding to discrete regions of proteins has facilitated the understanding of protein structure-activity relationships. Short peptides can also be used as powerful therapeutic agents. However, in many instances, small peptides are prone to rapid degradation or aggregation and may lack the conformation required to mimic the functional motifs of the protein. For peptides to function as pharmacologically active agents, efficient production or expression, high solubility, and retention of biological activity through purification and storage steps are required. We report here the design, expression, and functional analysis of eight engineered GST proteins (denoted GSHKTs) in which peptides ranging in size from 8 to 16 amino acids and derived from human high molecular weight kininogen (HK) domain 5 were inserted into GST (between Gly-49 and Leu-50). Peptides derived from HK are known to inhibit cell proliferation, angiogenesis, and tumor metastasis, and the biological activity of the HK peptides was dramatically (&gt;50-fold) enhanced following insertion into GST. GSHKTs are soluble and easily purified from Escherichia coli by affinity chromatography. Functionally, these hybrid proteins cause inhibition of endothelial cell proliferation. Crystallographic analysis of GSHKT10 and GSHKT13 (harboring 10- and 13-residue HK peptides, respectively) showed that the overall GST structure was not perturbed. These results suggest that the therapeutic efficacy of short peptides can be enhanced by insertion into larger proteins that are easily expressed and purified and that GST may potentially be used as such a carrier.
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Chimeric glutathione S-transferases containing inserts of kininogen peptides: potential novel protein therapeutics.,Bentley AA, Merkulov SM, Peng Y, Rozmarynowycz R, Qi X, Pusztai-Carey M, Merrick WC, Yee VC, McCrae KR, Komar AA J Biol Chem. 2012 Jun 22;287(26):22142-50. Epub 2012 May 10. PMID:22577144<ref>PMID:22577144</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4ecb" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Glutathione S-transferase|Glutathione S-transferase]]
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*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Blood fluke]]
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[[Category: Homo sapiens]]
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[[Category: Glutathione transferase]]
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[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Amber, A B]]
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[[Category: Schistosoma japonicum]]
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[[Category: Anton, A K]]
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[[Category: Amber AB]]
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[[Category: Keith, R M]]
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[[Category: Anton AK]]
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[[Category: Marianne, P C]]
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[[Category: Keith RM]]
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[[Category: Rita, R]]
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[[Category: Marianne P-C]]
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[[Category: Sergei, M M]]
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[[Category: Rita R]]
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[[Category: Vivien, Y]]
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[[Category: Sergei MM]]
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[[Category: William, C M]]
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[[Category: Vivien Y]]
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[[Category: Xiaoping, Q]]
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[[Category: William CM]]
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[[Category: Yi, P]]
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[[Category: Xiaoping Q]]
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[[Category: Protein binding]]
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[[Category: Yi P]]
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[[Category: Transferase]]
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Current revision

Chimeric GST Containing Inserts of Kininogen Peptides

PDB ID 4ecb

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Proteopedia Page Contributors and Editors (what is this?)

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