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Dihydropteroate synthase
From Proteopedia
(Difference between revisions)
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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='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. | 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. | ||
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| + | ==3D structures of dihydropteroate synthase== | ||
| + | [[Dihydropteroate synthase 3D structures]] | ||
</StructureSection> | </StructureSection> | ||
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**[[1ad1]], [[4hb7]] – SaDHPS - ''Staphylococcus aureus'' <br /> | **[[1ad1]], [[4hb7]] – SaDHPS - ''Staphylococcus aureus'' <br /> | ||
| + | **[[6clu]], [[6clv]] - SaDHPS (mutant)<br /> | ||
**[[1ajz]] – EcDHPS – ''Escherichia coli''<br /> | **[[1ajz]] – EcDHPS – ''Escherichia coli''<br /> | ||
**[[1tws]], [[3v5o]] – BaDHPS – ''Bacillus anthracis''<br /> | **[[1tws]], [[3v5o]] – BaDHPS – ''Bacillus anthracis''<br /> | ||
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**[[4o1e]], [[4o1f]] – DhDHPS + tetrahydrofolate derivative<br /> | **[[4o1e]], [[4o1f]] – DhDHPS + tetrahydrofolate derivative<br /> | ||
**[[6day]] - DHPS + PABA – ''Xanthomonas albilineans''<br /> | **[[6day]] - DHPS + PABA – ''Xanthomonas albilineans''<br /> | ||
| + | **[[6omz]] - DHPS + pterin-monophosphate – ''Mycobacterium smegmatis''<br /> | ||
*DHPS ternary complexes | *DHPS ternary complexes | ||
Revision as of 09:13, 10 June 2019
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3D structures of dihydropteroate synthase
Updated on 10-June-2019
References
- ↑ Vinnicombe HG, Derrick JP. Dihydropteroate synthase from Streptococcus pneumoniae: characterization of substrate binding order and sulfonamide inhibition. Biochem Biophys Res Commun. 1999 May 19;258(3):752-7. doi:, 10.1006/bbrc.1999.0695. PMID:10329458 doi:http://dx.doi.org/10.1006/bbrc.1999.0695
- ↑ 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
