HDNO_PAENI
ID HDNO_PAENI Reviewed; 458 AA.
AC P08159; Q8GAG1;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 2.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=(R)-6-hydroxynicotine oxidase {ECO:0000305};
DE EC=1.5.3.6 {ECO:0000269|PubMed:2680607, ECO:0000269|PubMed:31046245, ECO:0000269|PubMed:4628374, ECO:0000269|PubMed:4965794, ECO:0000269|PubMed:5849820};
DE AltName: Full=6-hydroxy-D-nicotine oxidase {ECO:0000303|PubMed:3622516};
DE Short=6-HDNO {ECO:0000303|PubMed:3622516};
DE AltName: Full=D-6-hydroxynicotine oxidase {ECO:0000303|PubMed:4965794};
DE Short=DHNO {ECO:0000303|PubMed:31046245};
GN Name=6-hdno {ECO:0000312|EMBL:CAD47970.1};
OS Paenarthrobacter nicotinovorans (Arthrobacter nicotinovorans).
OG Plasmid pAO1.
OC Bacteria; Actinobacteria; Micrococcales; Micrococcaceae; Paenarthrobacter.
OX NCBI_TaxID=29320;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3622516; DOI=10.1111/j.1432-1033.1987.tb13338.x;
RA Brandsch R., Hinkkanen A.E., Mauch L., Nagursky H., Decker K.;
RT "6-hydroxy-D-nicotine oxidase of Arthrobacter oxidans. Gene structure of
RT the flavoenzyme and its relationship to 6-hydroxy-L-nicotine oxidase.";
RL Eur. J. Biochem. 167:315-320(1987).
RN [2]
RP SEQUENCE REVISION.
RA Brandsch R.;
RL Submitted (SEP-1990) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 49919 / DSM 420 / JCM 3874 / NBRC 15511; PLASMID=pAO1;
RX PubMed=12618462; DOI=10.1128/jb.185.6.1976-1986.2003;
RA Igloi G.L., Brandsch R.;
RT "Sequence of the 165-kilobase catabolic plasmid pAO1 from Arthrobacter
RT nicotinovorans and identification of a pAO1-dependent nicotine uptake
RT system.";
RL J. Bacteriol. 185:1976-1986(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, AND INDUCTION.
RX PubMed=5849820; DOI=10.1016/s0926-6593(65)80155-2;
RA Decker K., Bleeg H.;
RT "Induction and purification of stereospecific nicotine oxidizing enzymes
RT from Arthrobacter oxidans.";
RL Biochim. Biophys. Acta 105:313-324(1965).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=4965794; DOI=10.1111/j.1432-1033.1967.tb19507.x;
RA Decker K., Dai V.D.;
RT "Mechanism and specifcity of L- and D-6-hydroxynicotine oxidase.";
RL Eur. J. Biochem. 3:132-138(1967).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=4628374; DOI=10.1111/j.1432-1033.1972.tb01968.x;
RA Bruehmueller M., Moehler H., Decker K.;
RT "Covalently bound flavin in D-6-hydroxynicotine oxidase from Arthrobacter
RT oxidans. Purification and properties of D-6-hydroxynicotine oxidase.";
RL Eur. J. Biochem. 29:143-151(1972).
RN [7]
RP COFACTOR.
RX PubMed=5083098; DOI=10.1111/j.1432-1033.1972.tb01969.x;
RA Moehler H., Bruehmueller M., Decker K.;
RT "Covalently bound flavin in D-6-hydroxynicotine oxidase from Arthrobacter
RT oxidans. Identification of the 8-(N-3-histidyl)-riboflavin-linkage between
RT FAD and apoenzyme.";
RL Eur. J. Biochem. 29:152-155(1972).
RN [8]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=4019415; DOI=10.1128/jb.163.2.792-795.1985;
RA Swafford J.R., Reeves H.C., Brandsch R.;
RT "Localization of the enantiozymes of 6-hydroxy-nicotine oxidase in
RT Arthrobacter oxidans by electron immunochemistry.";
RL J. Bacteriol. 163:792-795(1985).
RN [9]
RP CATALYTIC ACTIVITY, COFACTOR, FLAVIN BINDING AT HIS-71, AND MUTAGENESIS OF
RP HIS-71.
RX PubMed=2680607; DOI=10.1016/0014-5793(89)81792-2;
RA Mauch L., Bichler V., Brandsch R.;
RT "Site-directed mutagenesis of the FAD-binding histidine of 6-hydroxy-D-
RT nicotine oxidase. Consequences on flavinylation and enzyme activity.";
RL FEBS Lett. 257:86-88(1989).
RN [10]
RP COFACTOR, FLAVIN BINDING AT HIS-71, AND MUTAGENESIS OF ARG-67 AND SER-68.
RX PubMed=2115879; DOI=10.1016/s0021-9258(19)38220-1;
RA Mauch L., Bichler V., Brandsch R.;
RT "Lysine can replace arginine 67 in the mediation of covalent attachment of
RT FAD to histidine 71 of 6-hydroxy-D-nicotine oxidase.";
RL J. Biol. Chem. 265:12761-12762(1990).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, AND MUTAGENESIS OF
RP LYS-347; GLU-349 AND GLU-351.
RX PubMed=31046245; DOI=10.1021/acs.biochem.9b00297;
RA Fitzpatrick P.F., Dougherty V., Subedi B., Quilantan J., Hinck C.S.,
RA Lujan A.I., Tormos J.R.;
RT "Mechanism of the flavoprotein D-6-hydroxynicotine oxidase: substrate
RT specificity, pH and solvent isotope effects, and roles of key active-site
RT residues.";
RL Biochemistry 58:2534-2541(2019).
RN [12] {ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG}
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF SER-433 MUTANT IN COMPLEXES WITH
RP FAD, COFACTOR, FLAVIN BINDING AT HIS-71, AND SUBUNIT.
RX PubMed=16095622; DOI=10.1016/j.jmb.2005.07.041;
RA Koetter J.W., Schulz G.E.;
RT "Crystal structure of 6-hydroxy-D-nicotine oxidase from Arthrobacter
RT nicotinovorans.";
RL J. Mol. Biol. 352:418-428(2005).
CC -!- FUNCTION: Involved in the degradation of D-nicotine (PubMed:5849820,
CC PubMed:4628374). Catalyzes the oxidation of (R)-6-hydroxynicotine (6-
CC hydroxy-D-nicotine) to 6-hydroxypseudooxynicotine (PubMed:5849820,
CC PubMed:4965794, PubMed:4628374, PubMed:2680607, PubMed:31046245).
CC Oxidation of the pyrrolidine ring of (R)-6-hydroxynicotine leads to the
CC formation of the optically inactive 6-hydroxy-N-methylmyosmine, which
CC hydrolyzes spontaneously to 6-hydroxypseudooxynicotine (PubMed:4965794,
CC PubMed:4628374, PubMed:31046245). Acts with absolute stereospecificity
CC on the D-form of 6-hydroxynicotine (PubMed:4965794, PubMed:4628374).
CC Shows lower activity with (R)-6-hydroxynornicotine, and weak activity
CC with (R)-4-(1-methylpyrrolidine-2-yl)phenol, (R)-6-chloronicotine and
CC (R)-nicotine (PubMed:31046245). {ECO:0000269|PubMed:2680607,
CC ECO:0000269|PubMed:31046245, ECO:0000269|PubMed:4628374,
CC ECO:0000269|PubMed:4965794, ECO:0000269|PubMed:5849820}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-6-hydroxynicotine + H2O + O2 = 6-hydroxypseudooxynicotine
CC + H2O2; Xref=Rhea:RHEA:10012, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:58413, ChEBI:CHEBI:58682; EC=1.5.3.6;
CC Evidence={ECO:0000269|PubMed:2680607, ECO:0000269|PubMed:31046245,
CC ECO:0000269|PubMed:4628374, ECO:0000269|PubMed:4965794,
CC ECO:0000269|PubMed:5849820};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10013;
CC Evidence={ECO:0000269|PubMed:2680607, ECO:0000269|PubMed:31046245,
CC ECO:0000269|PubMed:4628374, ECO:0000269|PubMed:4965794,
CC ECO:0000269|PubMed:5849820};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-6-hydroxynicotine + O2 = 6-hydroxy-N-methylmyosmine +
CC H2O2; Xref=Rhea:RHEA:46988, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:58413, ChEBI:CHEBI:87164;
CC Evidence={ECO:0000269|PubMed:31046245, ECO:0000305|PubMed:4628374,
CC ECO:0000305|PubMed:4965794};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46989;
CC Evidence={ECO:0000269|PubMed:31046245, ECO:0000305|PubMed:4628374,
CC ECO:0000305|PubMed:4965794};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:16095622, ECO:0000269|PubMed:2115879,
CC ECO:0000269|PubMed:2680607, ECO:0000269|PubMed:4628374,
CC ECO:0000269|PubMed:5083098};
CC Note=Binds 1 FAD per subunit (PubMed:4628374, PubMed:16095622). The FAD
CC is covalently bound to the protein (PubMed:4628374, PubMed:5083098,
CC PubMed:2680607, PubMed:2115879, PubMed:16095622).
CC {ECO:0000269|PubMed:16095622, ECO:0000269|PubMed:2115879,
CC ECO:0000269|PubMed:2680607, ECO:0000269|PubMed:4628374,
CC ECO:0000269|PubMed:5083098};
CC -!- ACTIVITY REGULATION: Inhibited by (S)-6-hydroxynicotine
CC (PubMed:5849820, PubMed:4965794, PubMed:4628374). Inhibited by high
CC concentrations of phenanthroline (PubMed:4628374).
CC {ECO:0000269|PubMed:4628374, ECO:0000269|PubMed:4965794,
CC ECO:0000269|PubMed:5849820}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.1 mM for (R)-6-hydroxynicotine {ECO:0000269|PubMed:5849820};
CC KM=0.05 mM for (R)-6-hydroxynicotine {ECO:0000269|PubMed:4628374};
CC pH dependence:
CC Fairly stable at neutral or alkaline pH.
CC {ECO:0000269|PubMed:4628374};
CC Temperature dependence:
CC Inactivated at temperatures above 45 degrees Celsius.
CC {ECO:0000269|PubMed:4628374};
CC -!- PATHWAY: Alkaloid degradation; nicotine degradation; 6-
CC hydroxypseudooxynicotine from nicotine (R-isomer route): step 2/2.
CC {ECO:0000305|PubMed:5849820}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:16095622,
CC ECO:0000269|PubMed:4628374}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:4019415}.
CC -!- INDUCTION: Induced in the presence of D-nicotine (PubMed:5849820).
CC Expressed during stationary phase (PubMed:4019415).
CC {ECO:0000269|PubMed:4019415, ECO:0000269|PubMed:5849820}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD47970.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X05999; CAA29416.1; -; Genomic_DNA.
DR EMBL; AJ507836; CAD47970.1; ALT_INIT; Genomic_DNA.
DR PIR; S00087; DEIQHN.
DR RefSeq; WP_016359481.1; NC_021229.1.
DR RefSeq; YP_007988796.1; NC_021229.1.
DR PDB; 2BVF; X-ray; 1.92 A; A/B=1-458.
DR PDB; 2BVG; X-ray; 3.18 A; A/B/C/D=1-458.
DR PDB; 2BVH; X-ray; 2.90 A; A/B/C/D=1-458.
DR PDBsum; 2BVF; -.
DR PDBsum; 2BVG; -.
DR PDBsum; 2BVH; -.
DR AlphaFoldDB; P08159; -.
DR SMR; P08159; -.
DR UniPathway; UPA00106; UER00488.
DR EvolutionaryTrace; P08159; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0018530; F:(R)-6-hydroxynicotine oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019608; P:nicotine catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR016164; FAD-linked_Oxase-like_C.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR InterPro; IPR006093; Oxy_OxRdtase_FAD_BS.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF55103; SSF55103; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
DR PROSITE; PS00862; OX2_COVAL_FAD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Cytoplasm; FAD; Flavoprotein;
KW Nucleotide-binding; Oxidoreductase; Plasmid.
FT CHAIN 1..458
FT /note="(R)-6-hydroxynicotine oxidase"
FT /id="PRO_0000128157"
FT DOMAIN 33..204
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 67..73
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG,
FT ECO:0007744|PDB:2BVH"
FT BINDING 129..130
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG,
FT ECO:0007744|PDB:2BVH"
FT BINDING 134..137
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG,
FT ECO:0007744|PDB:2BVH"
FT BINDING 144
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG,
FT ECO:0007744|PDB:2BVH"
FT BINDING 195
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG,
FT ECO:0007744|PDB:2BVH"
FT BINDING 413
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG,
FT ECO:0007744|PDB:2BVH"
FT BINDING 450
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0007744|PDB:2BVF, ECO:0007744|PDB:2BVG,
FT ECO:0007744|PDB:2BVH"
FT MOD_RES 71
FT /note="Pros-8alpha-FAD histidine"
FT /evidence="ECO:0000269|PubMed:16095622,
FT ECO:0000269|PubMed:2115879, ECO:0000269|PubMed:2680607"
FT MUTAGEN 67
FT /note="R->A: No FAD incorporation."
FT /evidence="ECO:0000269|PubMed:2115879"
FT MUTAGEN 67
FT /note="R->K: No effect on FAD incorporation, but reduces
FT activity."
FT /evidence="ECO:0000269|PubMed:2115879"
FT MUTAGEN 68
FT /note="S->A: No effect on FAD incorporation or on
FT activity."
FT /evidence="ECO:0000269|PubMed:2115879"
FT MUTAGEN 71
FT /note="H->C,Y,S: No FAD incorporation, abolishes or
FT diminishes significantly the activity."
FT /evidence="ECO:0000269|PubMed:2680607"
FT MUTAGEN 347
FT /note="K->M: 2 to 3-fold decrease in kcat/Kamine and small
FT decrease in kcat with (R)-6-hydroxynicotine as substrate."
FT /evidence="ECO:0000269|PubMed:31046245"
FT MUTAGEN 349
FT /note="E->A: 20-fold decrease in kcat/Kamine and 4-fold
FT decrease in kcat with (R)-6-hydroxynicotine as substrate.
FT Large increase in the Kd value for (R)-6-hydroxynicotine."
FT /evidence="ECO:0000269|PubMed:31046245"
FT MUTAGEN 349
FT /note="E->Q: 220-fold decrease in kcat/Kamine and 8-fold
FT decrease in kcat with (R)-6-hydroxynicotine as substrate.
FT Large increase in the Kd value for (R)-6-hydroxynicotine."
FT /evidence="ECO:0000269|PubMed:31046245"
FT MUTAGEN 351
FT /note="E->Q: 3800-fold decrease in kcat/Kamine and 100-fold
FT decrease in kcat with (R)-6-hydroxynicotine as substrate.
FT Large increase in the Kd value for (R)-6-hydroxynicotine."
FT /evidence="ECO:0000269|PubMed:31046245"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:2BVH"
FT HELIX 23..27
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 47..60
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:2BVF"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 110..118
FT /evidence="ECO:0007829|PDB:2BVF"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:2BVG"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 169..177
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 193..200
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 208..215
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 219..235
FT /evidence="ECO:0007829|PDB:2BVF"
FT TURN 236..239
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 266..277
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 292..302
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 310..318
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 322..330
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 331..335
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:2BVF"
FT TURN 340..343
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 344..351
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 370..377
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:2BVH"
FT TURN 382..385
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 386..400
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 404..408
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 419..426
FT /evidence="ECO:0007829|PDB:2BVF"
FT HELIX 428..441
FT /evidence="ECO:0007829|PDB:2BVF"
FT STRAND 449..451
FT /evidence="ECO:0007829|PDB:2BVF"
SQ SEQUENCE 458 AA; 48786 MW; 6783E444D66DC841 CRC64;
MSSKLATPLS IQGEVIYPDD SGFDAIANIW DGRHLQRPSL IARCLSAGDV AKSVRYACDN
GLEISVRSGG HNPNGYATND GGIVLDLRLM NSIHIDTAGS RARIGGGVIS GDLVKEAAKF
GLAAVTGMHP KVGFCGLALN GGVGFLTPKY GLASDNILGA TLVTATGDVI YCSDDERPEL
FWAVRGAGPN FGVVTEVEVQ LYELPRKMLA GFITWAPSVS ELAGLLTSLL DALNEMADHI
YPSVFVGVDE NRAPSVTVCV GHLGGLDIAE RDIARLRGLG RTVSDSIAVR SYDEVVALNA
EVGSFEDGMS NLWIDREIAM PNARFAEAIA GNLDKFVSEP ASGGSVKLEI EGMPFGNPKR
TPARHRDAMG VLALAEWSGA APGSEKYPEL ARELDAALLR AGVTTSGFGL LNNNSEVTAE
MVAEVYKPEV YCRLAAVKRE YDPENRFRHN YNIDPEGS
