6fe0

From Proteopedia

(Difference between revisions)

Current revision

Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide.

Structural highlights

6fe0 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.91Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAH9_HUMAN Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.^[1]

Publication Abstract from PubMed

Human carbonic anhydrase (CA) IX has emerged as a promising anticancer target and a diagnostic biomarker for solid hypoxic tumors. Novel fluorinated CA IX inhibitors exhibited up to 50 pM affinity towards the recombinant human CA IX, selectivity over other CAs, and direct binding to Zn(II) in the active site of CA IX inducing novel conformational changes as determined by X-ray crystallography. Mass spectrometric gas-analysis confirmed the CA IX-based mechanism of the inhibitors in a CRISPR/Cas9-mediated CA IX knockout in HeLa cells. Hypoxia-induced extracellular acidification was significantly reduced in HeLa, H460, MDA-MB-231, and A549 cells exposed to the compounds, with the IC50 values up to 1.29 nM. A decreased clonogenic survival was observed when hypoxic H460 3D spheroids were incubated with our lead compound. These novel compounds are therefore promising agents for CA IX-specific therapy.

Novel fluorinated carbonic anhydrase IX inhibitors reduce hypoxia-induced acidification and clonogenic survival of cancer cells.,Kazokaite J, Niemans R, Dudutiene V, Becker HM, Leitans J, Zubriene A, Baranauskiene L, Gondi G, Zeidler R, Matuliene J, Tars K, Yaromina A, Lambin P, Dubois LJ, Matulis D Oncotarget. 2018 Jun 1;9(42):26800-26816. doi: 10.18632/oncotarget.25508., eCollection 2018 Jun 1. PMID:29928486^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hilvo M, Baranauskiene L, Salzano AM, Scaloni A, Matulis D, Innocenti A, Scozzafava A, Monti SM, Di Fiore A, De Simone G, Lindfors M, Janis J, Valjakka J, Pastorekova S, Pastorek J, Kulomaa MS, Nordlund HR, Supuran CT, Parkkila S. Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes. J Biol Chem. 2008 Oct 10;283(41):27799-809. doi: 10.1074/jbc.M800938200. Epub, 2008 Aug 13. PMID:18703501 doi:http://dx.doi.org/10.1074/jbc.M800938200
↑ Kazokaite J, Niemans R, Dudutiene V, Becker HM, Leitans J, Zubriene A, Baranauskiene L, Gondi G, Zeidler R, Matuliene J, Tars K, Yaromina A, Lambin P, Dubois LJ, Matulis D. Novel fluorinated carbonic anhydrase IX inhibitors reduce hypoxia-induced acidification and clonogenic survival of cancer cells. Oncotarget. 2018 Jun 1;9(42):26800-26816. doi: 10.18632/oncotarget.25508., eCollection 2018 Jun 1. PMID:29928486 doi:http://dx.doi.org/10.18632/oncotarget.25508

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fe0"

Categories: Homo sapiens | Large Structures | Leitans J | Tars K

@@ Line 1: / Line 1: @@
 ==Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide.==
-<StructureSection load='6fe0' size='340' side='right' caption='[[6fe0]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
+<StructureSection load='6fe0' size='340' side='right'caption='[[6fe0]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fe0]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FE0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FE0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fe0]] is a 4 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=6FE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FE0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=V90:2-(CYCLOOCTYLAMINO)-3,5,6-TRIFLUORO-4-[(2-HYDROXYETHYL)SULFANYL]BENZENESULFONAMIDE'>V90</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.91&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V90:2-(CYCLOOCTYLAMINO)-3,5,6-TRIFLUORO-4-[(2-HYDROXYETHYL)SULFANYL]BENZENESULFONAMIDE'>V90</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6fe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fe0 OCA], [http://pdbe.org/6fe0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fe0 RCSB], [http://www.ebi.ac.uk/pdbsum/6fe0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fe0 ProSAT]</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=6fe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fe0 OCA], [https://pdbe.org/6fe0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fe0 RCSB], [https://www.ebi.ac.uk/pdbsum/6fe0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fe0 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CAH9_HUMAN CAH9_HUMAN]] Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.<ref>PMID:18703501</ref>
+[https://www.uniprot.org/uniprot/CAH9_HUMAN CAH9_HUMAN] Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.<ref>PMID:18703501</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6fe0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Carbonate dehydratase]]
+[[Category: Homo sapiens]]
-[[Category: Leitans, J]]
+[[Category: Large Structures]]
-[[Category: Tars, K]]
+[[Category: Leitans J]]
-[[Category: Lyase]]
+[[Category: Tars K]]

6fe0

From Proteopedia

Current revision

Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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