Molecule Information

General Information of the Molecule (ID: Mol00887)

• Name: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) ,Candida albicans
• Synonyms: GSC1; EC 2.4.1.34
• Molecule Type: Protein
• Gene Name: GSC1
• Sequence:
  MSYNDNNNHYYDPNQQGGMPPHQGGEGYYQQQYDDMGQQPHQQDYYDPNAQYQQQPYDMD
  GYQDQANYGGQPMNAQGYNADPEAFSDFSYGGQTPGTPGYDQYGTQYTPSQMSYGGDPRS
  SGASTPIYGGQGQGYDPTQFNMSSNLPYPAWSADPQAPIKIEHIEDIFIDLTNKFGFQRD
  SMRNMFDYFMTLLDSRSSRMSPAQALLSLHADYIGGDNANYRKWYFSSQQDLDDSLGFAN
  MTLGKIGRKARKASKKSKKARKAAEEHGQDVDALANELEGDYSLEAAEIRWKAKMNSLTP
  EERVRDLALYLLIWGEANQVRFTPECLCYIYKSATDYLNSPLCQQRQEPVPEGDYLNRVI
  TPLYRFIRSQVYEIYDGRFVKREKDHNKVIGYDDVNQLFWYPEGISRIIFEDGTRLVDIP
  QEERFLKLGEVEWKNVFFKTYKEIRTWLHFVTNFNRIWIIHGTIYWMYTAYNSPTLYTKH
  YVQTINQQPLASSRWAACAIGGVLASFIQILATLFEWIFVPREWAGAQHLSRRMLFLVLI
  FLLNLVPPVYTFQITKLVIYSKSAYAVSIVGFFIAVATLVFFAVMPLGGLFTSYMNKRSR
  RYIASQTFTANYIKLKGLDMWMSYLLWFLVFLAKLVESYFFSTLSLRDPIRNLSTMTMRC
  VGEVWYKDIVCRNQAKIVLGLMYLVDLLLFFLDTYMWYIICNCIFSIGRSFYLGISILTP
  WRNIFTRLPKRIYSKILATTEMEIKYKPKVLISQIWNAIVISMYREHLLAIDHVQKLLYH
  QVPSEIEGKRTLRAPTFFVSQDDNNFETEFFPRNSEAERRISFFAQSLATPMPEPLPVDN
  MPTFTVFTPHYSEKILLSLREIIREDDQFSRVTLLEYLKQLHPVEWDCFVKDTKILAEET
  AAYENGDDSEKLSEDGLKSKIDDLPFYCIGFKSAAPEYTLRTRIWASLRSQTLYRTVSGF
  MNYARAIKLLYRVENPELVQYFGGDPEGLELALERMARRKFRFLVSMQRLSKFKDDEMEN
  AEFLLRAYPDLQIAYLDEEPALNEDEEPRVYSALIDGHCEMLENGRRRPKFRVQLSGNPI
  LGDGKSDNQNHAVIFHRGEYIQLIDANQDNYLEECLKIRSVLAEFEEMNVEHVNPYAPNL
  KSEDNNTKKDPVAFLGAREYIFSENSGVLGDVAAGKEQTFGTLFARTLAQIGGKLHYGHP
  DFLNATFMLTRGGVSKAQKGLHLNEDIYAGMNAMMRGGKIKHCEYYQCGKGRDLGFGSIL
  NFTTKIGAGMGEQMLSREYFYLGTQLPLDRFLSFYYGHPGFHINNLFIQLSLQVFILVLG
  NLNSLAHEAIMCSYNKDVPVTDVLYPFGCYNIAPAVDWIRRYTLSIFIVFFISFIPLVVQ
  ELIERGVWKAFQRFVRHFISMSPFFEVFVAQIYSSSVFTDLTVGGARYISTGRGFATSRI
  PFSILYSRFADSSIYMGARLMLILLFGTVSHWQAPLLWFWASLSALMFSPFIFNPHQFAW
  EDFFLDYRDFIRWLSRGNTKWHRNSWIGYVRLSRSRITGFKRKLTGDVSEKAAGDASRAH
  RSNVLFADFLPTLIYTAGLYVAYTFINAQTGVTSYPYEINGSTDPQPVNSTLRLIICALA
  PVVIDMGCLGVCLAMACCAGPMLGLCCKKTGAVIAGVAHGVAVIVHIIFFIVMWVTEGFN
  FARLMLGIATMIYVQRLLFKFLTLCFLTREFKNDKANTAFWTGKWYNTGMGWMAFTQPSR
  EFVAKIIEMSEFAGDFVLAHIILFCQLPLLFIPLVDRWHSMMLFWLKPSRLIRPPIYSLK
  QARLRKRMVRKYCVLYFAVLILFIVIIVAPAVASGQIAVDQFANIGGSGSIADGLFQPRN
  VSNNDTGNHRPKTYTWSYLSTRFTGSTTPYSTNPFRV
• Uniprot ID: O13428_CANAX

Kingdom: Fungi
Phylum: Ascomycota
Class: Saccharomycetes
Order: Saccharomycetales
Family: Debaryomycetaceae
Genus: Candida
Species: Candida albicans

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: Candida albicans infection [1]

• Resistant Disease: Candida albicans infection [ICD-11: 1F23.Y]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.S645Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida tropicalis strain NR3; 5482
• In Vivo Model: DBA/2J murine model of disseminated candidiasis; DBA/2N murine model of disseminated candidiasis; Mus musculus
• 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: Candida albicans infection [1]

• Resistant Disease: Candida albicans infection [ICD-11: 1F23.Y]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.S645F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida albicans strain; 5476
• In Vivo Model: DBA/2J murine model of disseminated candidiasis; DBA/2N murine model of disseminated candidiasis; Mus musculus
• 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: Candida albicans infection [2]

• Resistant Disease: Candida albicans infection [ICD-11: 1F23.Y]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.S645P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida albicans strain; 5476
• Experiment for Molecule Alteration: NGS sequencing assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Amino acid changes in FkS1 may contribute to Candida albicans emerging caspofungin resistance.

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: Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1. Antimicrob Agents Chemother. 2006 Jun;50(6):2058-63. doi: 10.1128/AAC.01653-05.