7cxx
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==Structural insights into novel mechanisms of inhibition of the major b-carbonic anhydrase CafB from the pathogenic fungus Aspergillus fumigatus (disulfide-bonded form)== | ==Structural insights into novel mechanisms of inhibition of the major b-carbonic anhydrase CafB from the pathogenic fungus Aspergillus fumigatus (disulfide-bonded form)== | ||
| - | <StructureSection load='7cxx' size='340' side='right'caption='[[7cxx]]' scene=''> | + | <StructureSection load='7cxx' size='340' side='right'caption='[[7cxx]], [[Resolution|resolution]] 2.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CXX FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CXX FirstGlance]. <br> | ||
| - | </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=7cxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cxx OCA], [https://pdbe.org/7cxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cxx RCSB], [https://www.ebi.ac.uk/pdbsum/7cxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cxx ProSAT]</span></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]] 2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7cxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cxx OCA], [https://pdbe.org/7cxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cxx RCSB], [https://www.ebi.ac.uk/pdbsum/7cxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cxx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In fungi the beta-class of carbonic anhydrases (beta-CAs) are zinc metalloenzymes that are essential for growth, survival, differentiation, and virulence. Aspergillus fumigatus is the most important pathogen responsible for invasive aspergillosis and possesses two major beta-CAs, CafA and CafB. Recently we reported the biochemical characterization and 1.8 A crystal structure of CafA. Here, we report a crystallographic analysis of CafB revealing the mechanism of enzyme catalysis and establish the relationship of this enzyme to other beta-CAs. While CafA has a typical open conformation, CafB, when exposed to acidic pH and/or an oxidative environment, has a novel type of active site in which a disulfide bond is formed between two zinc-ligating cysteines, expelling the zinc ion and stabilizing the inactive form of the enzyme. Based on the structural data, we generated an oxidation-resistant mutant (Y159A) of CafB. The crystal structure of the mutant under reducing conditions retains a catalytic zinc at the expected position, tetrahedrally coordinated by three residues (C57, H113 and C116) and an aspartic acid (D59), and replacing the zinc-bound water molecule in the closed form. Furthermore, the active site of CafB crystals grown under zinc-limiting conditions has a novel conformation in which the solvent-exposed catalytic cysteine (C116) is flipped out of the metal coordination sphere, facilitating release of the zinc ion. Taken together, our results suggest that A. fumigatus use sophisticated activity-inhibiting strategies to enhance its survival during infection. | ||
| + | |||
| + | Structural insights into novel mechanisms of inhibition of the major beta-carbonic anhydrase CafB from the pathogenic fungus Aspergillus fumigatus.,Kim S, Yeon J, Sung J, Kim NJ, Hong S, Jin MS J Struct Biol. 2021 Mar;213(1):107700. doi: 10.1016/j.jsb.2021.107700. Epub 2021 , Feb 3. PMID:33545350<ref>PMID:33545350</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7cxx" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structural insights into novel mechanisms of inhibition of the major b-carbonic anhydrase CafB from the pathogenic fungus Aspergillus fumigatus (disulfide-bonded form)
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Categories: Large Structures | Hong S | Jin MS | Kim NJ | Kim S | Sung J | Yeon J
