CP51B_ASPFU
ID CP51B_ASPFU Reviewed; 524 AA.
AC E9QY26;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Sterol 14-alpha demethylase cyp51B {ECO:0000303|PubMed:11427550};
DE EC=1.14.14.154 {ECO:0000269|PubMed:18191972, ECO:0000269|PubMed:26269599, ECO:0000269|PubMed:26459890, ECO:0000269|PubMed:28461309, ECO:0000269|PubMed:29439966};
DE AltName: Full=Cytochrome P450 monooxygenase 51B {ECO:0000303|PubMed:11427550};
DE AltName: Full=Ergosterol biosynthesis protein 11B {ECO:0000303|PubMed:11427550};
GN Name=cyp51B {ECO:0000303|PubMed:11427550}; ORFNames=AFUA_7G03740;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION.
RX PubMed=9184358; DOI=10.1093/jac/39.5.597;
RA Venkateswarlu K., Kelly S.L.;
RT "Stereoselective interaction of SCH 39304, a triazole, with sterol 14alpha-
RT demethylase of Aspergillus fumigatus.";
RL J. Antimicrob. Chemother. 39:597-601(1997).
RN [3]
RP IDENTIFICATION.
RX PubMed=11427550; DOI=10.1128/jcm.39.7.2431-2438.2001;
RA Mellado E., Diaz-Guerra T.M., Cuenca-Estrella M., Rodriguez-Tudela J.L.;
RT "Identification of two different 14-alpha sterol demethylase-related genes
RT (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus
RT species.";
RL J. Clin. Microbiol. 39:2431-2438(2001).
RN [4]
RP FUNCTION.
RX PubMed=12543662; DOI=10.1128/aac.47.2.577-581.2003;
RA Mann P.A., Parmegiani R.M., Wei S.Q., Mendrick C.A., Li X., Loebenberg D.,
RA DiDomenico B., Hare R.S., Walker S.S., McNicholas P.M.;
RT "Mutations in Aspergillus fumigatus resulting in reduced susceptibility to
RT posaconazole appear to be restricted to a single amino acid in the
RT cytochrome P450 14alpha-demethylase.";
RL Antimicrob. Agents Chemother. 47:577-581(2003).
RN [5]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=16110826; DOI=10.1080/13693780400029114;
RA Ferreira M.E., Colombo A.L., Paulsen I., Ren Q., Wortman J., Huang J.,
RA Goldman M.H., Goldman G.H.;
RT "The ergosterol biosynthesis pathway, transporter genes, and azole
RT resistance in Aspergillus fumigatus.";
RL Med. Mycol. 43:S313-S319(2005).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=18191972; DOI=10.1016/j.steroids.2007.11.005;
RA Alcazar-Fuoli L., Mellado E., Garcia-Effron G., Lopez J.F., Grimalt J.O.,
RA Cuenca-Estrella J.M., Rodriguez-Tudela J.L.;
RT "Ergosterol biosynthesis pathway in Aspergillus fumigatus.";
RL Steroids 73:339-347(2008).
RN [7]
RP INDUCTION.
RX PubMed=23208831; DOI=10.1093/jac/dks451;
RA Buied A., Moore C.B., Denning D.W., Bowyer P.;
RT "High-level expression of cyp51B in azole-resistant clinical Aspergillus
RT fumigatus isolates.";
RL J. Antimicrob. Chemother. 68:512-514(2013).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=26459890; DOI=10.1128/aac.01806-15;
RA Warrilow A.G., Parker J.E., Price C.L., Nes W.D., Kelly S.L., Kelly D.E.;
RT "In Vitro biochemical study of CYP51-mediated azole resistance in
RT Aspergillus fumigatus.";
RL Antimicrob. Agents Chemother. 59:7771-7778(2015).
RN [9]
RP FUNCTION.
RX PubMed=28224386; DOI=10.1007/s11274-017-2214-9;
RA Jahanshiri Z., Shams-Ghahfarokhi M., Asghari-Paskiabi F., Saghiri R.,
RA Razzaghi-Abyaneh M.;
RT "alpha-Bisabolol inhibits Aspergillus fumigatus Af239 growth via affecting
RT microsomal delta24-sterol methyltransferase as a crucial enzyme in
RT ergosterol biosynthesis pathway.";
RL World J. Microbiol. Biotechnol. 33:55-55(2017).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=29439966; DOI=10.1128/aac.01941-17;
RA Colley T., Sehra G., Chowdhary A., Alanio A., Kelly S.L., Kizawa Y.,
RA Armstrong-James D., Fisher M.C., Warrilow A.G.S., Parker J.E., Kelly D.E.,
RA Kimura G., Nishimoto Y., Sunose M., Onions S., Crepin D., Lagasse F.,
RA Crittall M., Shannon J., McConville M., King-Underwood J., Naylor A.,
RA Bretagne S., Murray J., Ito K., Strong P., Rapeport G.;
RT "In vitro and in vivo efficacy of a novel and long-acting fungicidal azole,
RT PC1244, on Aspergillus fumigatus infection.";
RL Antimicrob. Agents Chemother. 62:0-0(2018).
RN [11] {ECO:0007744|PDB:4UYL, ECO:0007744|PDB:4UYM}
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 50-518 IN COMPLEX WITH INHIBITOR
RP AND HEME, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=26269599; DOI=10.1074/jbc.m115.677310;
RA Hargrove T.Y., Wawrzak Z., Lamb D.C., Guengerich F.P., Lepesheva G.I.;
RT "Structure-functional characterization of cytochrome P450 sterol 14alpha-
RT demethylase (CYP51B) from Aspergillus fumigatus and molecular basis for the
RT development of antifungal drugs.";
RL J. Biol. Chem. 290:23916-23934(2015).
RN [12] {ECO:0007744|PDB:5FRB}
RP X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS) OF 50-518 IN COMPLEX WITH INHIBITOR
RP AND HEME, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=28461309; DOI=10.1128/aac.00570-17;
RA Hargrove T.Y., Garvey E.P., Hoekstra W.J., Yates C.M., Wawrzak Z.,
RA Rachakonda G., Villalta F., Lepesheva G.I.;
RT "Crystal structure of the new investigational drug candidate VT-1598 in
RT complex with Aspergillus fumigatus sterol 14alpha-demethylase provides
RT insights into its broad-spectrum antifungal activity.";
RL Antimicrob. Agents Chemother. 61:0-0(2017).
RN [13] {ECO:0007744|PDB:6CR2}
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 51-518 IN COMPLEX WITH INHIBITOR,
RP AND FUNCTION.
RX PubMed=29894182; DOI=10.1021/acs.jmedchem.8b00641;
RA Friggeri L., Hargrove T.Y., Wawrzak Z., Blobaum A.L., Rachakonda G.,
RA Lindsley C.W., Villalta F., Nes W.D., Botta M., Guengerich F.P.,
RA Lepesheva G.I.;
RT "Sterol 14alpha-demethylase structure-based design of VNI ((R)- N-(1-(2,4-
RT Dichlorophenyl)-2-(1 H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-
RT yl)benzamide)) derivatives to target fungal infections: synthesis,
RT biological evaluation, and crystallographic analysis.";
RL J. Med. Chem. 61:5679-5691(2018).
CC -!- FUNCTION: Sterol 14-alpha demethylase; part of the third module of
CC ergosterol biosynthesis pathway that includes the late steps of the
CC pathway (PubMed:18191972, PubMed:26459890, PubMed:29439966,
CC PubMed:9184358). Demethylates eburicol to yield 4,4,24-trimethyl
CC ergosta-8,14,24(28)-trienol (PubMed:18191972, PubMed:26459890,
CC PubMed:29439966, PubMed:9184358). The third module or late pathway
CC involves the ergosterol synthesis itself through consecutive reactions
CC that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly,
CC the squalene synthase erg9 catalyzes the condensation of 2 farnesyl
CC pyrophosphate moieties to form squalene, which is the precursor of all
CC steroids. Squalene synthase is crucial for balancing the incorporation
CC of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene
CC synthesis. Secondly, squalene is converted into lanosterol by the
CC consecutive action of the squalene epoxidase erg1 and the lanosterol
CC synthase erg7. Then, the delta(24)-sterol C-methyltransferase erg6
CC methylates lanosterol at C-24 to produce eburicol. Eburicol is the
CC substrate of the sterol 14-alpha demethylase encoded by cyp51A and
CC cyp51B, to yield 4,4,24-trimethyl ergosta-8,14,24(28)-trienol. The C-14
CC reductase erg24 then reduces the C14=C15 double bond which leads to
CC 4,4-dimethylfecosterol. A sequence of further demethylations at C-4,
CC involving the C-4 demethylation complex containing the C-4 methylsterol
CC oxidases erg25A or erg25B, the sterol-4-alpha-carboxylate 3-
CC dehydrogenase erg26 and the 3-keto-steroid reductase erg27, leads to
CC the production of fecosterol via 4-methylfecosterol. The C-8 sterol
CC isomerase erg2 then catalyzes the reaction which results in
CC unsaturation at C-7 in the B ring of sterols and thus converts
CC fecosterol to episterol. The sterol-C5-desaturase erg3B then catalyzes
CC the introduction of a C-5 double bond in the B ring to produce 5-
CC dehydroepisterol. The 2 other sterol-C5-desaturases, erg3A and erg3C,
CC seem to be less important in ergosterol biosynthesis. The C-22 sterol
CC desaturase erg5 further converts 5-dehydroepisterol into ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double bond in
CC the sterol side chain. Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC is substrate of the C-24(28) sterol reductases erg4A and erg4B to
CC produce ergosterol. Possible alternative sterol biosynthetic pathways
CC might exist from fecosterol to ergosterol, depending on the activities
CC of the erg3 isoforms (PubMed:16110826, PubMed:18191972) (Probable).
CC {ECO:0000269|PubMed:18191972, ECO:0000269|PubMed:26459890,
CC ECO:0000269|PubMed:29439966, ECO:0000269|PubMed:9184358,
CC ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:18191972}.
CC -!- FUNCTION: As a target of azole drugs, plays a crucial role in azole
CC susceptibility. {ECO:0000269|PubMed:12543662,
CC ECO:0000269|PubMed:26269599, ECO:0000269|PubMed:28461309,
CC ECO:0000269|PubMed:29894182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4
CC H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154;
CC Evidence={ECO:0000269|PubMed:18191972, ECO:0000269|PubMed:26269599,
CC ECO:0000269|PubMed:26459890, ECO:0000269|PubMed:28461309,
CC ECO:0000269|PubMed:29439966};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000269|PubMed:18191972, ECO:0000269|PubMed:26269599,
CC ECO:0000269|PubMed:26459890, ECO:0000269|PubMed:28461309,
CC ECO:0000269|PubMed:29439966};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:26269599};
CC -!- ACTIVITY REGULATION: The activity is completely inhibited by miconazole
CC and reduced by voriconazole (6% substrate conversion), posaconazole
CC (10%), itraconazole (16%), (R)-N-(1-(2,4-dichlorophenyl)-2-(1H-
CC imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VNI)
CC (20%), and (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-
CC yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VFV) (31%). The
CC weakest inhibitory effect is observed with fluconazole
CC (PubMed:26459890, PubMed:26269599, PubMed:28461309). Activity is also
CC inhibited by ketoconazole, as well as by the azole-based drug
CC candidates VT-1161 and VT-1598 (PubMed:28461309). Activity is inhibited
CC by the novel and long-acting fungicidal azole PC1244 (PubMed:29439966).
CC {ECO:0000269|PubMed:26269599, ECO:0000269|PubMed:26459890,
CC ECO:0000269|PubMed:28461309, ECO:0000269|PubMed:29439966}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.8 uM for eburicol {ECO:0000269|PubMed:26269599};
CC KM=3.78 uM for obtusifoliol {ECO:0000269|PubMed:26269599};
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000269|PubMed:18191972, ECO:0000269|PubMed:26269599,
CC ECO:0000269|PubMed:28461309}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Over-expressed in azole-resistant clinical isolates.
CC {ECO:0000269|PubMed:23208831}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of erburicol.
CC {ECO:0000269|PubMed:18191972}.
CC -!- MISCELLANEOUS: In Aspergillus, the biosynthesis pathway of the sterol
CC precursors leading to the prevalent sterol ergosterol differs from
CC yeast. The ring system of lanosterol in S.cerevisiae is firstly
CC demethylised in three enzymatic steps leading to the intermediate
CC zymosterol and secondly a methyl group is added to zymosterol by the
CC sterol 24-C-methyltransferase to form fecosterol. In Aspergillus,
CC lanosterol is firstly transmethylated by the sterol 24-C-
CC methyltransferase leading to the intermediate eburicol and secondly
CC demethylated in three steps to form fecosterol.
CC {ECO:0000305|PubMed:18191972}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AAHF01000009; EAL87096.1; -; Genomic_DNA.
DR RefSeq; XP_749134.1; XM_744041.1.
DR PDB; 4UYL; X-ray; 2.81 A; A/B=50-518.
DR PDB; 4UYM; X-ray; 2.55 A; A/B=50-518.
DR PDB; 5FRB; X-ray; 2.99 A; A=50-518.
DR PDB; 6CR2; X-ray; 2.38 A; A/B=51-518.
DR PDBsum; 4UYL; -.
DR PDBsum; 4UYM; -.
DR PDBsum; 5FRB; -.
DR PDBsum; 6CR2; -.
DR AlphaFoldDB; E9QY26; -.
DR SMR; E9QY26; -.
DR STRING; 746128.CADAFUBP00008678; -.
DR EnsemblFungi; EAL87096; EAL87096; AFUA_7G03740.
DR GeneID; 3506370; -.
DR KEGG; afm:AFUA_7G03740; -.
DR VEuPathDB; FungiDB:Afu7g03740; -.
DR eggNOG; KOG0684; Eukaryota.
DR HOGENOM; CLU_001570_15_0_1; -.
DR InParanoid; E9QY26; -.
DR OMA; QRCVKET; -.
DR OrthoDB; 572303at2759; -.
DR UniPathway; UPA00768; -.
DR PHI-base; PHI:2535; -.
DR Proteomes; UP000002530; Chromosome 7.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008398; F:sterol 14-demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Metal-binding; Methyltransferase;
KW Monooxygenase; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..524
FT /note="Sterol 14-alpha demethylase cyp51B"
FT /id="PRO_0000448946"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 463
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0007744|PDB:4UYL, ECO:0007744|PDB:4UYM,
FT ECO:0007744|PDB:5FRB"
FT TURN 60..64
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 65..70
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 72..83
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:6CR2"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:4UYL"
FT HELIX 140..153
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 156..176
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 189..204
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 208..213
FT /evidence="ECO:0007829|PDB:6CR2"
FT TURN 214..217
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 218..225
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 226..229
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 242..266
FT /evidence="ECO:0007829|PDB:6CR2"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 276..282
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 294..325
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 327..341
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 350..353
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 357..370
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 376..380
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 387..390
FT /evidence="ECO:0007829|PDB:4UYM"
FT STRAND 397..401
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 403..407
FT /evidence="ECO:0007829|PDB:6CR2"
FT TURN 410..412
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 421..426
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 440..443
FT /evidence="ECO:0007829|PDB:4UYM"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:6CR2"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:4UYM"
FT HELIX 466..483
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 484..487
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 489..491
FT /evidence="ECO:0007829|PDB:4UYL"
FT STRAND 498..501
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 504..507
FT /evidence="ECO:0007829|PDB:6CR2"
FT STRAND 512..517
FT /evidence="ECO:0007829|PDB:6CR2"
SQ SEQUENCE 524 AA; 58931 MW; 156E9765D42FE0D1 CRC64;
MGLIAFILDG ICKHCSTQST WVLVGIGLLS ILAVSVIINV LQQLLFKNPH EPPVVFHWFP
FIGSTISYGI DPYKFFFDCR AKYGDIFTFI LLGKKTTVYL GTKGNDFILN GKLRDVCAEE
VYSPLTTPVF GRHVVYDCPN AKLMEQKKFV KYGLTSDALR SYVPLITDEV ESFVKNSPAF
QGHKGVFDVC KTIAEITIYT ASRSLQGKEV RSKFDSTFAE LYHNLDMGFA PINFMLPWAP
LPHNRKRDAA QRKLTETYME IIKARRQAGS KKDSEDMVWN LMSCVYKNGT PVPDEEIAHM
MIALLMAGQH SSSSTASWIV LRLATRPDIM EELYQEQIRV LGSDLPPLTY DNLQKLDLHA
KVIKETLRLH APIHSIIRAV KNPMAVDGTS YVIPTSHNVL SSPGVTARSE EHFPNPLEWN
PHRWDENIAA SAEDDEKVDY GYGLVSKGTN SPYLPFGAGR HRCIGEQFAY LQLGTITAVL
VRLFRFRNLP GVDGIPDTDY SSLFSKPLGR SFVEFEKRES ATKA
