Molecule Information

General Information of the Molecule (ID: Mol01048)

• Name: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) ,Saccharomyces cerevisiae
• Synonyms: Pleiotropic drug resistance protein 5; Suppressor of toxicity of sporidesmin; LEM1; STS1; YDR1; YOR153W
• Molecule Type: Protein
• Gene Name: PDR5
• Gene ID: 854324
• Sequence:
  MPEAKLNNNVNDVTSYSSASSSTENAADLHNYNGFDEHTEARIQKLARTLTAQSMQNSTQ
  SAPNKSDAQSIFSSGVEGVNPIFSDPEAPGYDPKLDPNSENFSSAAWVKNMAHLSAADPD
  FYKPYSLGCAWKNLSASGASADVAYQSTVVNIPYKILKSGLRKFQRSKETNTFQILKPMD
  GCLNPGELLVVLGRPGSGCTTLLKSISSNTHGFDLGADTKISYSGYSGDDIKKHFRGEVV
  YNAEADVHLPHLTVFETLVTVARLKTPQNRIKGVDRESYANHLAEVAMATYGLSHTRNTK
  VGNDIVRGVSGGERKRVSIAEVSICGSKFQCWDNATRGLDSATALEFIRALKTQADISNT
  SATVAIYQCSQDAYDLFNKVCVLDDGYQIYYGPADKAKKYFEDMGYVCPSRQTTADFLTS
  VTSPSERTLNKDMLKKGIHIPQTPKEMNDYWVKSPNYKELMKEVDQRLLNDDEASREAIK
  EAHIAKQSKRARPSSPYTVSYMMQVKYLLIRNMWRLRNNIGFTLFMILGNCSMALILGSM
  FFKIMKKGDTSTFYFRGSAMFFAILFNAFSSLLEIFSLYEARPITEKHRTYSLYHPSADA
  FASVLSEIPSKLIIAVCFNIIFYFLVDFRRNGGVFFFYLLINIVAVFSMSHLFRCVGSLT
  KTLSEAMVPASMLLLALSMYTGFAIPKKKILRWSKWIWYINPLAYLFESLLINEFHGIKF
  PCAEYVPRGPAYANISSTESVCTVVGAVPGQDYVLGDDFIRGTYQYYHKDKWRGFGIGMA
  YVVFFFFVYLFLCEYNEGAKQKGEILVFPRSIVKRMKKRGVLTEKNANDPENVGERSDLS
  SDRKMLQESSEEESDTYGEIGLSKSEAIFHWRNLCYEVQIKAETRRILNNVDGWVKPGTL
  TALMGASGAGKTTLLDCLAERVTMGVITGDILVNGIPRDKSFPRSIGYCQQQDLHLKTAT
  VRESLRFSAYLRQPAEVSIEEKNRYVEEVIKILEMEKYADAVVGVAGEGLNVEQRKRLTI
  GVELTAKPKLLVFLDEPTSGLDSQTAWSICQLMKKLANHGQAILCTIHQPSAILMQEFDR
  LLFMQRGGKTVYFGDLGEGCKTMIDYFESHGAHKCPADANPAEWMLEVVGAAPGSHANQD
  YYEVWRNSEEYRAVQSELDWMERELPKKGSITAAEDKHEFSQSIIYQTKLVSIRLFQQYW
  RSPDYLWSKFILTIFNQLFIGFTFFKAGTSLQGLQNQMLAVFMFTVIFNPILQQYLPSFV
  QQRDLYEARERPSRTFSWISFIFAQIFVEVPWNILAGTIAYFIYYYPIGFYSNASAAGQL
  HERGALFWLFSCAFYVYVGSMGLLVISFNQVAESAANLASLLFTMSLSFCGVMTTPSAMP
  RFWIFMYRVSPLTYFIQALLAVGVANVDVKCADYELLEFTPPSGMTCGQYMEPYLQLAKT
  GYLTDENATDTCSFCQISTTNDYLANVNSFYSERWRNYGIFICYIAFNYIAGVFFYWLAR
  VPKKNGKLSKK
• Function: Active efflux of weakly charged organic compounds of 90 cubic Angstroms to 300 cubic Angstroms surface volume. Confers resistance to numerous chemicals including cycloheximide, sulfomethuron methyl, steroids, antiseptics, antibiotics, anticancer, herbicides, mycotoxins, insecticides, ionophores, alkaloids, flavonoids, phenothiazines, organotin compounds, carbazoles, lysosomotropic aminoesters, detergents, rhodamines and other fluorophores, azoles and other antifungals. Exhibits nucleoside triphosphatase activity.
• Uniprot ID: PDR5_YEAST

Kingdom: Fungi
Phylum: Ascomycota
Class: Saccharomycetes
Order: Saccharomycetales
Family: Saccharomycetaceae
Genus: Saccharomyces
Species: Saccharomyces cerevisiae

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Cantharidin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Sacharomyces cerevisiae infection [1]

• Resistant Disease: Sacharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Resistant Drug: Cantharidin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: TRAMP-C2 cells; Prostate; Homo sapiens (Human); CVCL_3615
• Experiment for Molecule Alteration: Western blot analysis; Fluorescence microscopy assay
• Experiment for Drug Resistance: Spot dilution assay; Liquid media growth curve analysis; Colony forming unit (CFU) assay
• Mechanism Description: ABC transporter Pdr5 is required for cantharidin resistance in Saccharomyces cerevisiae. Cantharidin mediated upregulation of Pdr5 is majorly regulated by Pdr1, cantharidin induced the upregulation of both PDR1 and PDR5 genes., PDR5 is the main cantharidin resistance gene.

Capsaicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Fungal infection [2]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Capsaicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae S288C; 559292
• In Vitro Model: Yeast deletion strains; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: Capsaicin does not affect the growth rate signicantly but increases the lag period, the addition of capsaicin increased the lag period, especially that of the YOR153W (PDR5, a multi-drug resistance transporter) deletion strain.

Clotrimazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Fungal infection [3]

• Resistant Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Resistant Drug: Clotrimazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: Pdr5p is an important ABC transporter. It is a 170 kDa plasma membrane protein with 1511 amino acids in a single polypeptide chain. It effluxes a wide range of structurally and functionally diverse compounds, such as rhodamine 6-G, tetrapropyltin, cycloheximide, tritylimidazole, and clotrimazole. Loss-of-function mutations in the pdr5 gene cause profound drug hypersensitivity, while overexpression creates multidrug hyperresi.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.T257I
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.S1048V
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.N242K
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.H1068A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.G908S
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.G905S+p.G908S
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.G905S
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.G302D
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.G1040D
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.G1009C
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Disease Class: Fungal infection [3]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Clotrimazole
• Molecule Alteration: Missense mutation; p.E1289K+p.Y1311S
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Yeast detapdr5 strain R-1; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Determined spectrophotometrically assay
• Mechanism Description: The double mutation Gly905Ser/Gly908Ser that is located in the Walker A motif of NBD2. Apparently the double mutation disrupts the ATP catalytic cycle since the cells bearing it are sensitive to all Pdr5p drugs. Other NBD mutations result in a differential sensitivity. Those mutations include Asn242Lys, Thr257Ile, Gly302Asp, Gly1009Cys, Gly1040Asp, Ser1048Val, and His1.

Lovastatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Fungal infection [4]

• Sensitive Disease: Fungal infection [ICD-11: 1F29-1F2F]
• Sensitive Drug: Lovastatin
• Molecule Alteration: Deletion mutation; Deleteion
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain Y12409; 4932
• In Vitro Model: Saccharomyces cerevisiae strain Y13029; 4932
• In Vitro Model: Saccharomyces cerevisiae strain Y13951; 4932
• In Vitro Model: Saccharomyces cerevisiae strain Y14381; 4932
• In Vitro Model: Sarcoma tissue; .
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: Spot Test
• Mechanism Description: We investigated the susceptibility to lovastatin of S. cerevisiae strains deleted for PDR genes, responsible for exporting hydrophobic and amphiphilic drugs, such as lovastatin. Strains deleted for the genes tested, PDR1, PDR3, PDR5 and SNQ2, exhibited remarkably different phenotypes, with deletion of PDR5 causing the highest sensitivity to lovastatin. The study helped clarifying which pdr mutants to use in studies of physiological actions of statins in yeast.

References

• Ref 1: ABC transporter Pdr5 is required for cantharidin resistance in Saccharomyces cerevisiae .Biochem Biophys Res Commun. 2021 May 14;553:141-147. doi: 10.1016/j.bbrc.2021.03.074. Epub 2021 Mar 24. 10.1016/j.bbrc.2021.03.074
• Ref 2: Studies on the antimicrobial mechanisms of capsaicin using yeast DNA microarray. Biosci Biotechnol Biochem. 2002 Mar;66(3):532-6. doi: 10.1271/bbb.66.532.
• Ref 3: Toward understanding the mechanism of action of the yeast multidrug resistance transporter Pdr5p: a molecular modeling study. J Struct Biol. 2011 Feb;173(2):333-44. doi: 10.1016/j.jsb.2010.10.012. Epub 2010 Oct 27.
• Ref 4: Sensitivity to lovastatin of Saccharomyces cerevisiae strains deleted for pleiotropic drug resistance (PDR) genes .J Mol Microbiol Biotechnol. 2011;20(4):191-5. doi: 10.1159/000329068. Epub 2011 Jul 12. 10.1159/000329068