Journal:JBSD:24
From Proteopedia
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Drug resistance has been an urgent problem that severely limits the therapy of current clinical microbial diseases. Sometimes, it generally correlates with mutations to the dihydropteroate synthase (DHPS) gene. | Drug resistance has been an urgent problem that severely limits the therapy of current clinical microbial diseases. Sometimes, it generally correlates with mutations to the dihydropteroate synthase (DHPS) gene. | ||
In the current study, we focus on the molecular dynamic behaviors and binding free energy calculations of <scene name='50/509381/Cv/10'>wild-type (wt)</scene> form and <scene name='50/509381/Cv/11'>mutated forms</scene> ''B. anthracis'' dihydropteroate synthase (BaDHPS) to search for the relationship between mutation and drug resistance. <span style="color:khaki;background-color:black;font-weight:bold;">Wt-BaDHPS is colored in khaki</span>, mutated <span style="color:lime;background-color:black;font-weight:bold;">D184N complex is in green</span> and <span style="color:cyan;background-color:black;font-weight:bold;">K220Q complex is in cyan</span>. | In the current study, we focus on the molecular dynamic behaviors and binding free energy calculations of <scene name='50/509381/Cv/10'>wild-type (wt)</scene> form and <scene name='50/509381/Cv/11'>mutated forms</scene> ''B. anthracis'' dihydropteroate synthase (BaDHPS) to search for the relationship between mutation and drug resistance. <span style="color:khaki;background-color:black;font-weight:bold;">Wt-BaDHPS is colored in khaki</span>, mutated <span style="color:lime;background-color:black;font-weight:bold;">D184N complex is in green</span> and <span style="color:cyan;background-color:black;font-weight:bold;">K220Q complex is in cyan</span>. | ||
| - | After 20ns MD simulations on the <scene name='50/509381/Cv/12'>wt form and mutated form enzymes</scene>, it is obvious that <scene name=' | + | After 20ns MD simulations on the <scene name='50/509381/Cv/12'>wt form and mutated form enzymes</scene>, it is obvious that <scene name='50/509381/8/1'>mutation D184N and K220Q have much lower binding affinity to the inhibitor DHP-STZ than the wt form enzyme</scene>. Only Loop 1, Loop 2 and Loop 7 are colored, ligand DHP-STZ is colored in the same color as the corresponding protein: for <span style="color:khaki;background-color:black;font-weight:bold;">Wt-BaDHPS is colored in khaki</span>, for mutated <span style="color:lime;background-color:black;font-weight:bold;">D184N complex is in green</span> and for <span style="color:cyan;background-color:black;font-weight:bold;">K220Q complex is in cyan</span>. Mutation will cause conformational change, which mainly locate on some loop region around the binding site (Loop 1, Loop 2 and Loop 7). These results may be helpful for further drug resistance and de novo drug design investigations. |
</StructureSection> | </StructureSection> | ||
Current revision
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- ↑ Chu WT, Zhang JL, Zheng QC, Chen L, Xue Q, Zhang HX. Insights into the drug resistance induced by the BaDHPS mutations: molecular dynamic simulations and MM/GBSA studies. J Biomol Struct Dyn. 2012 Oct 2. PMID:23030549 doi:10.1080/07391102.2012.726529
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