Molecule Information

General Information of the Molecule (ID: Mol00888)

• Name: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) ,Saccharomyces cerevisiae
• Synonyms: 1;3-beta-D-glucan-UDP glucosyltransferase; Calcineurin dependent protein 1; Calcofluor white hypersensitivity protein 53; Echinocandin target gene protein 1; FK506 sensitivity protein 1; Glucan synthase of cerevisiae protein 1; Papulacandin B resistance protein 1; CND1; CWH53; ETG1; GLS1; GSC1; PBR1; YLR342W; L8300.6
• Molecule Type: Protein
• Gene Name: FKS1
• Gene ID: 851055
• Sequence:
  MNTDQQPYQGQTDYTQGPGNGQSQEQDYDQYGQPLYPSQADGYYDPNVAAGTEADMYGQQ
  PPNESYDQDYTNGEYYGQPPNMAAQDGENFSDFSSYGPPGTPGYDSYGGQYTASQMSYGE
  PNSSGTSTPIYGNYDPNAIAMALPNEPYPAWTADSQSPVSIEQIEDIFIDLTNRLGFQRD
  SMRNMFDHFMVLLDSRSSRMSPDQALLSLHADYIGGDTANYKKWYFAAQLDMDDEIGFRN
  MSLGKLSRKARKAKKKNKKAMEEANPEDTEETLNKIEGDNSLEAADFRWKAKMNQLSPLE
  RVRHIALYLLCWGEANQVRFTAECLCFIYKCALDYLDSPLCQQRQEPMPEGDFLNRVITP
  IYHFIRNQVYEIVDGRFVKRERDHNKIVGYDDLNQLFWYPEGIAKIVLEDGTKLIELPLE
  ERYLRLGDVVWDDVFFKTYKETRTWLHLVTNFNRIWVMHISIFWMYFAYNSPTFYTHNYQ
  QLVDNQPLAAYKWASCALGGTVASLIQIVATLCEWSFVPRKWAGAQHLSRRFWFLCIIFG
  INLGPIIFVFAYDKDTVYSTAAHVVAAVMFFVAVATIIFFSIMPLGGLFTSYMKKSTRRY
  VASQTFTAAFAPLHGLDRWMSYLVWVTVFAAKYSESYYFLVLSLRDPIRILSTTAMRCTG
  EYWWGAVLCKVQPKIVLGLVIATDFILFFLDTYLWYIIVNTIFSVGKSFYLGISILTPWR
  NIFTRLPKRIYSKILATTDMEIKYKPKVLISQVWNAIIISMYREHLLAIDHVQKLLYHQV
  PSEIEGKRTLRAPTFFVSQDDNNFETEFFPRDSEAERRISFFAQSLSTPIPEPLPVDNMP
  TFTVLTPHYAERILLSLREIIREDDQFSRVTLLEYLKQLHPVEWECFVKDTKILAEETAA
  YEGNENEAEKEDALKSQIDDLPFYCIGFKSAAPEYTLRTRIWASLRSQTLYRTISGFMNY
  SRAIKLLYRVENPEIVQMFGGNAEGLERELEKMARRKFKFLVSMQRLAKFKPHELENAEF
  LLRAYPDLQIAYLDEEPPLTEGEEPRIYSALIDGHCEILDNGRRRPKFRVQLSGNPILGD
  GKSDNQNHALIFYRGEYIQLIDANQDNYLEECLKIRSVLAEFEELNVEQVNPYAPGLRYE
  EQTTNHPVAIVGAREYIFSENSGVLGDVAAGKEQTFGTLFARTLSQIGGKLHYGHPDFIN
  ATFMTTRGGVSKAQKGLHLNEDIYAGMNAMLRGGRIKHCEYYQCGKGRDLGFGTILNFTT
  KIGAGMGEQMLSREYYYLGTQLPVDRFLTFYYAHPGFHLNNLFIQLSLQMFMLTLVNLSS
  LAHESIMCIYDRNKPKTDVLVPIGCYNFQPAVDWVRRYTLSIFIVFWIAFVPIVVQELIE
  RGLWKATQRFFCHLLSLSPMFEVFAGQIYSSALLSDLAIGGARYISTGRGFATSRIPFSI
  LYSRFAGSAIYMGARSMLMLLFGTVAHWQAPLLWFWASLSSLIFAPFVFNPHQFAWEDFF
  LDYRDYIRWLSRGNNQYHRNSWIGYVRMSRARITGFKRKLVGDESEKAAGDASRAHRTNL
  IMAEIIPCAIYAAGCFIAFTFINAQTGVKTTDDDRVNSVLRIIICTLAPIAVNLGVLFFC
  MGMSCCSGPLFGMCCKKTGSVMAGIAHGVAVIVHIAFFIVMWVLESFNFVRMLIGVVTCI
  QCQRLIFHCMTALMLTREFKNDHANTAFWTGKWYGKGMGYMAWTQPSRELTAKVIELSEF
  AADFVLGHVILICQLPLIIIPKIDKFHSIMLFWLKPSRQIRPPIYSLKQTRLRKRMVKKY
  CSLYFLVLAIFAGCIIGPAVASAKIHKHIGDSLDGVVHNLFQPINTTNNDTGSQMSTYQS
  HYYTHTPSLKTWSTIK
• Function: Alternate catalytic subunit of the 1,3-beta-glucan synthase (GS). Synthesizes 1,3-beta-glucan, a major structural component of the yeast cell wall. Involved in cell wall synthesis, maintenance and cell wall remodeling.
• Uniprot ID: FKS1_YEAST

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

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Caspofungin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Saccharomyces cerevisiae infection [1]

• Resistant Disease: Saccharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.F639I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Saccharomyces cerevisiae strain; 4932
• Experiment for Molecule Alteration: Site-directed mutagenesis; MLST assay
• Experiment for Drug Resistance: Liquid broth microdilution assay
• Mechanism Description: One group of amino acid substitutions, in the Fks proteins of S. cerevisiae (F639I, V641k, D646Y) and C. albicans (S645F, S645P, S645Y), maps to a short conserved region of ScFks1p and CaFks1p, which lead to caspofungin resistance in the S. cerevisiae and C. albicans as well as C.krusei.

Disease Class: Saccharomyces cerevisiae infection [1]

• Resistant Disease: Saccharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.V641K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Saccharomyces cerevisiae strain; 4932
• Experiment for Molecule Alteration: Site-directed mutagenesis; MLST assay
• Experiment for Drug Resistance: Liquid broth microdilution assay
• Mechanism Description: One group of amino acid substitutions, in the Fks proteins of S. cerevisiae (F639I, V641k, D646Y) and C. albicans (S645F, S645P, S645Y), maps to a short conserved region of ScFks1p and CaFks1p, which lead to caspofungin resistance in the S. cerevisiae and C. albicans as well as C.krusei.

Disease Class: Saccharomyces cerevisiae infection [1]

• Resistant Disease: Saccharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.D646Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Saccharomyces cerevisiae strain; 4932
• Experiment for Molecule Alteration: Site-directed mutagenesis; MLST assay
• Experiment for Drug Resistance: Liquid broth microdilution assay
• Mechanism Description: One group of amino acid substitutions, in the Fks proteins of S. cerevisiae (F639I, V641k, D646Y) and C. albicans (S645F, S645P, S645Y), maps to a short conserved region of ScFks1p and CaFks1p, which lead to caspofungin resistance in the S. cerevisiae and C. albicans as well as C.krusei.

Discontinued Drug(s) 1 drug(s) in total

Arborcandin C

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Saccharomyces cerevisiae infection [2]

• Resistant Disease: Saccharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Resistant Drug: Arborcandin C
• Molecule Alteration: Missense mutation; p.N470K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Saccharomyces cerevisiae strain; 4932
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Broth macrodilution assay
• Mechanism Description: FkS1 mutations responsible for selective resistance of Saccharomyces cerevisiae to the novel 1,3-beta-glucan synthase inhibitor arborcandin C.

Disease Class: Saccharomyces cerevisiae infection [2]

• Resistant Disease: Saccharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Resistant Drug: Arborcandin C
• Molecule Alteration: Missense mutation; p.L642S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Saccharomyces cerevisiae strain; 4932
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Broth macrodilution assay
• Mechanism Description: FkS1 mutations responsible for selective resistance of Saccharomyces cerevisiae to the novel 1,3-beta-glucan synthase inhibitor arborcandin C.

References

• Ref 1: Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother. 2005 Aug;49(8):3264-73. doi: 10.1128/AAC.49.8.3264-3273.2005.
• Ref 2: FKS1 mutations responsible for selective resistance of Saccharomyces cerevisiae to the novel 1,3-beta-glucan synthase inhibitor arborcandin C. Antimicrob Agents Chemother. 2004 Jan;48(1):319-22. doi: 10.1128/AAC.48.1.319-322.2004.