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| <StructureSection load='1tws' size='350' side='right' scene='' caption='Dihydropteroate synthase complex with sulfate (PDB code [[1tws]])'> | | <StructureSection load='1tws' size='350' side='right' scene='' caption='Dihydropteroate synthase complex with sulfate (PDB code [[1tws]])'> |
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| | __TOC__ |
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| | ==Function== |
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| '''Dihydropteroate synthase''' (DHPS) catalyzes the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to para-aminobenzoic acid (PABA) to form 7,8-dihydropteroate. DHPs is a key enzyme in folate synthesis. Folate is necessary for nucleic acid synthesis. DHPS is found in bacteria and not in eukaryotes. Hence, it makes a target to sulfonamide antibiotics<ref>PMID:10329458</ref> Some DHPS contain a dihydro-6-hydroxymethylpterin pyrophosphokinase domain at their N terminal and are named PPPK-DHPS. | | '''Dihydropteroate synthase''' (DHPS) catalyzes the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to para-aminobenzoic acid (PABA) to form 7,8-dihydropteroate. DHPs is a key enzyme in folate synthesis. Folate is necessary for nucleic acid synthesis. DHPS is found in bacteria and not in eukaryotes. Hence, it makes a target to sulfonamide antibiotics<ref>PMID:10329458</ref> Some DHPS contain a dihydro-6-hydroxymethylpterin pyrophosphokinase domain at their N terminal and are named PPPK-DHPS. |
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| === Insights into the drug resistance induced by the BaDHPS mutations: molecular dynamic simulations and MM/GBSA studies <ref>doi 10.1080/07391102.2012.726529</ref>===
| | == Insights into the drug resistance induced by the BaDHPS mutations: molecular dynamic simulations and MM/GBSA studies <ref>doi 10.1080/07391102.2012.726529</ref>== |
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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. |
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| </StructureSection> | | </StructureSection> |
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| ==3D structures of dihydropteroate synthase==
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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| {{#tree:id=OrganizedByTopic|openlevels=0|
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| *DHPS
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| **[[1ad1]], [[4hb7]] – SaDHPS - ''Staphylococcus aureus'' <br />
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| **[[6clu]], [[6clv]] - SaDHPS (mutant)<br />
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| **[[1ajz]] – EcDHPS – ''Escherichia coli''<br />
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| **[[1tws]], [[3v5o]] – BaDHPS – ''Bacillus anthracis''<br />
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| **[[2dqw]] - TtDHPS – ''Thermus thermophilus''<br />
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| **[[2vef]] - SpDHPS – ''Streptococcus pneumoniae''<br />
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| **[[2vp8]] – MtDHPS – ''Mycobacterium tuberculosis''<br />
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| **[[2y5j]] – BcDHPS – ''Burkholderia cenocepacia''<br />
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| **[[3tzn]] – YpDHPS – ''Yersinia pestis''<br />
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| **[[4o0q]] – DhDHPS – ''Desulfitobacterium hafniense''<br />
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| **[[5umg]] - DHPS – ''Klebsiella pneumoniae''<br />
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| **[[5usw]] - DHPS – ''Vibrio fischeri''<br />
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| **[[5vis]] - DHPS – soil metagenome<br />
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| *DHPS binary complexes
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| **[[1ad4]] – SaDHPS + pterin-pyrophosphate<br />
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| **[[1aj2]] – EcDHPS + dihydro-pterin-methanyl-phosphonophosphate<br />
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| **[[5u0v]] - EcDHPS + nitrosoisocytosine inhibitor<br />
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| **[[5u0w]], [[5u0y]], [[5u0z]], [[5u11]], [[5u12]], [[5u13]], [[5u14]], [[5v79]], [[5v7a]] - EcDHPS + guanine inhibitor<br />
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| **[[5u10]] - EcDHPS + pteroic acid inhibitor<br />
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| **[[1eye]] - MtDHPS + pterin-methyl-phosphate<br />
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| **[[1tww]] - BaDHPS + hydroxymethylpterin-diphosphate<br />
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| **[[1twz]] - BaDHPS + pterin-methyl-phosphate<br />
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| **[[1tx0]] - BaDHPS + pteroic acid<br />
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| **[[1tx2]], [[3h21]], [[3h22]], [[3h23]], [[3h24]], [[3h26]], [[3h2a]], [[3h2c]], [[3h2e]], [[3h2f]], [[3h2m]], [[3h2n]], [[3h2o]], [[4d8z]], [[4d9p]], [[4dai]], [[4db7]], [[4d8a]], [[4daf]], [[4nhv]], [[4nil]], [[4nir]], [[4nl1]] - BaDHPS + inhibitor<br />
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| **[[2dza]] - TtDHPS + PABA<br />
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| **[[2dzb]] - TtDHPS + hydroxymethylpterin-diphosphate<br />
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| **[[2veg]] - SpDHPS + pterin-methyl-phosphate<br />
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| **[[2y5s]] - BcDHPS + dihydro-pteroate<br />
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| **[[3tya]] - BaDHPS + dihydro-pteroate<br />
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| **[[3tyc]] - BaDHPS + amino-hydroxymethyl-dihydro-pteridinone<br />
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| **[[3tr9]] - DHPS + pteroic acid – ''Coxiella burnetii''<br />
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| **[[3tyu]] – YpDHPS + pteroic acid <br />
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| **[[5jq9]] - YpDHPS + sulfonamide inhibitor<br />
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| **[[4o1e]], [[4o1f]] – DhDHPS + tetrahydrofolate derivative<br />
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| **[[6day]] - DHPS + PABA – ''Xanthomonas albilineans''<br />
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| **[[6omz]] - DHPS + pterin-monophosphate – ''Mycobacterium smegmatis''<br />
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| *DHPS ternary complexes
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| **[[1aj0]] – EcDHPS + sulfanilamide + amino-methyldiene-dihydro-pteridinone<br />
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| **[[3tyb]] - BaDHPS + hydroxybenzoic acid + amino-hydroxymethyl-dihydro-pteridinone<br />
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| **[[3tyd]] - BaDHPS + pyrophosphate+ amino-hydroxymethyl-dihydro-pteridinone<br />
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| **[[3tye]] - BaDHPS + sulfa derivative + amino-hydroxymethyl-dihydro-pteridinone<br />
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| **[[3tyz]] - YpDHPS + pyrophosphate + PABA + amino-hydroxymethyl-dihydro-pteridinone<br />
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| **[[3tzf]] - YpDHPS + sulfa derivative + hydroxymethylpterin-diphosphate<br />
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| *Bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophsphokinase-DHPS
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| **[[3mcm]], [[3mcn]] – FtPPPK-DHPS – ''Francisella tulerensis''<br />
| | ==References== |
| **[[3mco]] - FtPPPK-DHPS + amino-hydroxymethyl-dihydro-pteridinone + methyladenosine triphosphate<br />
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| **[[2bmb]] - PPPK-DHPS + pterin-methyl-phosphate - yeast
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| }}
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| '''References'''
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| <references/> | | <references/> |
| [[Category:Topic Page]] | | [[Category:Topic Page]] |