3fqv: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='3fqv' size='340' side='right'caption='[[3fqv]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
<StructureSection load='3fqv' size='340' side='right'caption='[[3fqv]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3fqv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staab Staab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FQV FirstGlance]. <br>
<table><tr><td colspan='2'>[[3fqv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_RF122 Staphylococcus aureus RF122]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FQV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=11F:5-[(3S)-3-(2-METHOXYBIPHENYL-4-YL)BUT-1-YN-1-YL]-6-METHYLPYRIMIDINE-2,4-DIAMINE'>11F</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 1.85&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3f0b|3f0b]], [[3f0u|3f0u]], [[3f0q|3f0q]], [[3f0v|3f0v]], [[3f0s|3f0s]], [[3f0x|3f0x]], [[3fq0|3fq0]], [[3fqc|3fqc]], [[3fqf|3fqf]], [[3fqo|3fqo]], [[3fqz|3fqz]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=11F:5-[(3S)-3-(2-METHOXYBIPHENYL-4-YL)BUT-1-YN-1-YL]-6-METHYLPYRIMIDINE-2,4-DIAMINE'>11F</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dfrB, SAB1281c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273036 STAAB])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=3fqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqv OCA], [https://pdbe.org/3fqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fqv RCSB], [https://www.ebi.ac.uk/pdbsum/3fqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqv 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=3fqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqv OCA], [https://pdbe.org/3fqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fqv RCSB], [https://www.ebi.ac.uk/pdbsum/3fqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqv ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/Q2YY41_STAAB Q2YY41_STAAB]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).[PIRNR:PIRNR000194]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 22: Line 18:
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fqv ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fqv ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Both hospital- and community-acquired Staphylococcus aureus infections have become major health concerns in terms of morbidity, suffering and cost. Trimethoprim-sulfamethoxazole (TMP-SMZ) is an alternative treatment for methicillin-resistant S. aureus (MRSA) infections. However, TMP-resistant strains have arisen with point mutations in dihydrofolate reductase (DHFR), the target for TMP. A single point mutation, F98Y, has been shown biochemically to confer the majority of this resistance to TMP. Using a structure-based approach, we have designed a series of novel propargyl-linked DHFR inhibitors that are active against several trimethoprim-resistant enzymes. We screened this series against wild-type and mutant (F98Y) S. aureus DHFR and found that several are active against both enzymes and specifically that the meta-biphenyl class of these inhibitors is the most potent. In order to understand the structural basis of this potency, we determined eight high-resolution crystal structures: four each of the wild-type and mutant DHFR enzymes bound to various propargyl-linked DHFR inhibitors. In addition to explaining the structure-activity relationships, several of the structures reveal a novel conformation for the cofactor, NADPH. In this new conformation that is predominantly associated with the mutant enzyme, the nicotinamide ring is displaced from its conserved location and three water molecules complete a network of hydrogen bonds between the nicotinamide ring and the protein. In this new position, NADPH has reduced interactions with the inhibitor. An equilibrium between the two conformations of NADPH, implied by their occupancies in the eight crystal structures, is influenced both by the ligand and the F98Y mutation. The mutation induced equilibrium between two NADPH-binding conformations may contribute to decrease TMP binding and thus may be responsible for TMP resistance.
Crystal structures of wild-type and mutant methicillin-resistant Staphylococcus aureus dihydrofolate reductase reveal an alternate conformation of NADPH that may be linked to trimethoprim resistance.,Frey KM, Liu J, Lombardo MN, Bolstad DB, Wright DL, Anderson AC J Mol Biol. 2009 Apr 17;387(5):1298-308. Epub 2009 Feb 26. PMID:19249312<ref>PMID:19249312</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3fqv" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Dihydrofolate reductase]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Staab]]
[[Category: Staphylococcus aureus RF122]]
[[Category: Anderson, A C]]
[[Category: Anderson AC]]
[[Category: Frey, K M]]
[[Category: Frey KM]]
[[Category: Liu, J]]
[[Category: Liu J]]
[[Category: Lombardo, M N]]
[[Category: Lombardo MN]]
[[Category: Oxidoreductase]]

Latest revision as of 12:50, 21 February 2024

Staphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(3-methoxy-4-phenylphenyl)but-1-ynyl]-6-methylpyrimidineStaphylococcus aureus F98Y mutant dihydrofolate reductase complexed with NADPH and 2,4-diamino-5-[3-(3-methoxy-4-phenylphenyl)but-1-ynyl]-6-methylpyrimidine

Structural highlights

3fqv is a 1 chain structure with sequence from Staphylococcus aureus RF122. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.85Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

3fqv, resolution 1.85Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3fqv&oldid=4064733"