|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3hj3' size='340' side='right'caption='[[3hj3]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='3hj3' size='340' side='right'caption='[[3hj3]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hj3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryho Cryho]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HJ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HJ3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hj3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryho Cryho]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HJ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HJ3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Chro.40506 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237895 CRYHO])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Chro.40506 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237895 CRYHO])</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=3hj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hj3 OCA], [http://pdbe.org/3hj3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hj3 RCSB], [http://www.ebi.ac.uk/pdbsum/3hj3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hj3 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=3hj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hj3 OCA], [https://pdbe.org/3hj3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hj3 RCSB], [https://www.ebi.ac.uk/pdbsum/3hj3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hj3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q5CGA3_CRYHO Q5CGA3_CRYHO]] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389] | + | [[https://www.uniprot.org/uniprot/Q5CGA3_CRYHO Q5CGA3_CRYHO]] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Structural highlights
Function
[Q5CGA3_CRYHO] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) from the protozoal parasite Cryptosporidium hominis is a potential molecular target for the design of antiparasitic therapies for AIDS-related opportunistic infections. The enzyme exists as a homodimer with each monomer containing a unique swap domain known as a "crossover helix" that binds in a cleft on the adjacent DHFR active site. This crossover helix is absent in species containing monofunctional forms of DHFR such as human. An in-depth understanding of protein-protein interactions between the crossover helix and adjacent DHFR active site that might modulate enzyme integrity or function would allow for insights into rational design of species-specific allosteric inhibitors. Mutational analysis coupled with structural studies and biophysical and kinetic characterization of crossover helix mutants identifies this domain as essential for full enzyme stability and catalytic activity, and pinpoints these effects to distinct faces of the crossover helix important in protein-protein interactions. Moreover, targeting this helical protein interaction with alpha-helix mimetics of the crossover helix leads to selective inhibition and destabilization of the C. hominis TS-DHFR enzyme, thus validating this region as a new avenue to explore for species-specific inhibitor design.
Exploring novel strategies for AIDS protozoal pathogens: alpha-helix mimetics targeting a key allosteric protein-protein interaction in TS-DHFR.,Martucci WE, Rodriguez JM, Vargo MA, Marr M, Hamilton AD, Anderson KS Medchemcomm. 2013 Sep;4(9). doi: 10.1039/C3MD00141E. PMID:24324854[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martucci WE, Rodriguez JM, Vargo MA, Marr M, Hamilton AD, Anderson KS. Exploring novel strategies for AIDS protozoal pathogens: alpha-helix mimetics targeting a key allosteric protein-protein interaction in TS-DHFR. Medchemcomm. 2013 Sep;4(9). doi: 10.1039/C3MD00141E. PMID:24324854 doi:http://dx.doi.org/10.1039/C3MD00141E
|
