View source for 7lvo


==Cryptococcus neoformans GAR synthetase==
<StructureSection load='7lvo' size='340' side='right'caption='[[7lvo]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lvo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_H99 Cryptococcus neoformans var. grubii H99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LVO FirstGlance]. <br>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=7lvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lvo OCA], [https://pdbe.org/7lvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lvo RCSB], [https://www.ebi.ac.uk/pdbsum/7lvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lvo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PUR2_CRYNH PUR2_CRYNH] Catalyzes the second and fifth step in the 'de novo' purine biosynthesis pathway; contains phosphoribosylamine--glycine ligase (GARS) and phosphoribosylformylglycinamidine cyclo-ligase (AIRS) activities.<ref>PMID:34416230</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cryptococcus neoformans is a fungus that causes life-threatening systemic mycoses. During infection of the human host, this pathogen experiences a major change in the availability of purines; the fungus can scavenge the abundant purines in its environmental niche of pigeon excrement, but must employ de novo biosynthesis in the purine-poor human CNS. Eleven sequential enzymatic steps are required to form the first purine base, IMP, an intermediate in the formation of ATP and GTP. Over the course of evolution, several gene fusion events led to the formation of multifunctional purine biosynthetic enzymes in most organisms, particularly the higher eukaryotes. In C. neoformans, phosphoribosyl-glycinamide synthetase (GARs) and phosphoribosyl-aminoimidazole synthetase (AIRs) are fused into a bifunctional enzyme, while the human ortholog is a trifunctional enzyme that also includes GAR transformylase. Here we functionally, biochemically, and structurally characterized C. neoformans GARs and AIRs to identify drug targetable features. GARs/AIRs are essential for de novo purine production and virulence in a murine inhalation infection model. Characterization of GARs enzymatic functional parameters showed that C. neoformans GARs/AIRs have lower affinity for substrates glycine and PRA compared with the trifunctional metazoan enzyme. The crystal structure of C. neoformans GARs revealed differences in the glycine- and ATP-binding sites compared with the Homo sapiens enzyme, while the crystal structure of AIRs shows high structural similarity compared with its H. sapiens ortholog as a monomer but differences as a dimer. The alterations in functional and structural characteristics between fungal and human enzymes could potentially be exploited for antifungal development.

Structural features of Cryptococcus neoformans bifunctional GAR/AIR synthetase may present novel antifungal drug targets.,Chua SMH, Wizrah MSI, Luo Z, Lim BYJ, Kappler U, Kobe B, Fraser JA J Biol Chem. 2021 Aug 17;297(4):101091. doi: 10.1016/j.jbc.2021.101091. PMID:34416230<ref>PMID:34416230</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lvo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Cryptococcus neoformans var. grubii H99]]
[[Category: Large Structures]]
[[Category: Chua SMH]]
[[Category: Fraser JA]]
[[Category: Kobe B]]
[[Category: Lim BYJ]]
[[Category: Luo Z]]