From Proteopedia
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| - | <Structure load='4riu' size='350' frame='true' align='right' caption='Human carbonic anhydrase 2 complex with saccharine derivative, glycerol and Zn+2 ions (grey) (PDB code [[4riu]])' scene='Insert optional scene name here' /> | + | <StructureSection load='4riu' size='350' side='right' scene='' caption='Human carbonic anhydrase 2 complex with saccharine derivative, glycerol and Zn+2 ions (grey) (PDB code [[4riu]])' pspeed='8'> |
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| | ==Description/Function== | | ==Description/Function== |
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| | <scene name='55/559112/Leu_198/1'>Leu 198</scene> | | <scene name='55/559112/Leu_198/1'>Leu 198</scene> |
| | <scene name='55/559112/Val_131/2'>Val 131</scene> | | <scene name='55/559112/Val_131/2'>Val 131</scene> |
| - | | + | </StructureSection> |
| | ==References== | | ==References== |
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Revision as of 09:55, 26 December 2019
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Description/Function
Human carbonic anydrase 2 is a one chain structure that is 260 amino acids long. It is a transmembrane homodimeric enzyme with an extracellularly positioned catalytic domain. 4RIU's functions include bone resorption, regulation of fluid secretion into anterior chamber of eye and catalyzing the hydration of CO2 to HCO3− and a proton.
Abbreviations
CA-carbonic anhydrase; Ki-inhibition constant; ZBG-zinc binding group
Ligands
3QR, Jmol GOL, Jmol ZN
Focal Points
Many cancers are made exceedingly invasive when tumors are subjected to hypoxic stresses triggered by a decrease of oxygen in the tumor’s microenvironment or by aspects involved with inflammation. Hypoxic stress increases tumor growth, metastasis, invasiveness and resistance to treatments. When under hypoxic stress the pH of the tumor’s microenvironment decreases while the pH inside the tumor stays fairly normal and when this differential environment is altered it is fatal to the tumor cells. Carbonic anhydrase IX influences the differential pH and when it is inhibited it decreases tumor growth and enhances the effectiveness of cancer treatments. Saccharin binds to CA IX with nano molar affinity and preferential binding thus inhibiting CA IX.
The SAC has a preference in binding to CA IX and CA XII over CA I and II. This is believed to be due to the substitution of PHE131 for Val in CA IX. It binds directly to the catalytic zinc of the CA IX-mimic displacing the zinc-bound OH-/H2O.
Critical Amino Acids
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References
Brian P. Mahon, Alex M. Hendon, Jenna M. Driscoll, Gregory M. Rankin, Sally-Ann Poulsen, Claudiu T. Supuran, Robert McKenna, Saccharin: A lead compound for structure-based drug design of carbonic anhydrase IX inhibitors, Bioorganic & Medicinal Chemistry, Volume 23, Issue 4, 15 February 2015, Pages 849-854, ISSN 0968-0896, http://dx.doi.org/10.1016/j.bmc.2014.12.030.
(http://www.sciencedirect.com/science/article/pii/S0968089614008785)
Authors
Elizabeth A. Dunlap, Preeti K. Deol
