6eha: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 ==Heme oxygenase 1 in complex with inhibitor==
-<StructureSection load='6eha' size='340' side='right' caption='[[6eha]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='6eha' size='340' side='right'caption='[[6eha]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6eha]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EHA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EHA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6eha]] is a 2 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=6EHA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EHA FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B5B:1-(3-imidazol-1-ylpropyl)-5-(2-methylpropyl)-4-phenyl-imidazole'>B5B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMOX1, HO, HO1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heme_oxygenase_(biliverdin-producing) Heme oxygenase (biliverdin-producing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.18 1.14.14.18] </span></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=6eha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eha OCA], [http://pdbe.org/6eha PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eha RCSB], [http://www.ebi.ac.uk/pdbsum/6eha PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eha ProSAT]</span></td></tr>
@@ Line 12: / Line 13: @@
 == Function ==
 [[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Heme oxygenase-1 (HO-1, HMOX1) degrades pro-oxidant heme into carbon monoxide (CO), ferrous ions (Fe(2+)) and biliverdin. The enzyme exerts multiple cytoprotective functions associated with the promotion of angiogenesis and counteraction of the detrimental effects of cellular stress which are crucial for the survival of both normal and tumor cells. Accordingly, in many tumor types, high expression of HO-1 correlates with poor prognosis and resistance to treatment, i.e. chemotherapy, suggesting inhibition of HO-1 as a possible antitumor approach. At the same time, the lack of selective and well-profiled inhibitors of HO-1 determines the unmet need for new modulators of this enzyme, with the potential to be used in either adjuvant therapy or as the stand-alone targeted therapeutics. In the current study, we provided novel inhibitors of HO-1 and validated the effect of pharmacological inhibition of HO activity by the imidazole-based inhibitor (SLV-11199) in human pancreatic (PANC-1) and prostate (DU-145) cancer cell lines. We demonstrated potent inhibition of HO activity in vitro and showed associated anticancer effectiveness of SLV-11199. Treatment with the tested compound led to decreased cancer cell viability and clonogenic potential. It has also sensitized the cancer cells to chemotherapy. In PANC-1cells, diminished HO activity resulted in down-regulation of pro-angiogenic factors like IL-8. Mechanistic investigations revealed that the treatment with SLV-11199 decreased cell migration and inhibited MMP-1 and MMP-9 expression. Moreover, it affected mesenchymal phenotype by regulating key modulators of the epithelial to mesenchymal transition (EMT) signalling axis. Finally, F-actin cytoskeleton and focal contacts were destabilized by the reported compound. Overall, the current study suggests a possible relevance of the tested novel inhibitor of HO activity as a potential anticancer compound. To support such utility, further investigation is still needed, especially in in vivo conditions.
+Development and characterization of a new inhibitor of heme oxygenase activity for cancer treatment.,Mucha O, Podkalicka P, Mikulski M, Barwacz S, Andrysiak K, Biela A, Mieczkowski M, Kachamakova-Trojanowska N, Ryszawy D, Bialas A, Szelazek B, Grudnik P, Majewska E, Michalik K, Jakubiec K, Bien M, Witkowska N, Gluza K, Ekonomiuk D, Sitarz K, Galezowski M, Brzozka K, Dubin G, Jozkowicz A, Dulak J, Loboda A Arch Biochem Biophys. 2019 Aug 15;671:130-142. doi: 10.1016/j.abb.2019.07.002., Epub 2019 Jul 2. PMID:31276659<ref>PMID:31276659</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6eha" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Heme oxygenase 3D structures|Heme oxygenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Grudnik, P]]
 [[Category: Mieczkowski, M]]
 [[Category: Heme oxygenase]]
 [[Category: Oxidoreductase]]