CAR_NOCIO
ID CAR_NOCIO Reviewed; 1174 AA.
AC Q6RKB1;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Carboxylic acid reductase {ECO:0000255|HAMAP-Rule:MF_02247, ECO:0000303|PubMed:15006821};
DE Short=CAR {ECO:0000255|HAMAP-Rule:MF_02247, ECO:0000303|PubMed:15006821};
DE EC=1.2.1.- {ECO:0000255|HAMAP-Rule:MF_02247};
DE AltName: Full=ATP/NADPH-dependent carboxylic acid reductase {ECO:0000255|HAMAP-Rule:MF_02247};
DE AltName: Full=Aryl aldehyde oxidoreductase {ECO:0000303|PubMed:9171390};
DE EC=1.2.1.30 {ECO:0000269|PubMed:17102130, ECO:0000269|PubMed:9171390, ECO:0000269|Ref.4};
GN Name=car {ECO:0000255|HAMAP-Rule:MF_02247};
OS Nocardia iowensis.
OC Bacteria; Actinobacteria; Corynebacteriales; Nocardiaceae; Nocardia.
OX NCBI_TaxID=204891;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], GENE NAME, FUNCTION, CATALYTIC ACTIVITY,
RP AND SUBSTRATE SPECIFICITY.
RC STRAIN=DSM 45197 / JCM 18299 / NRRL 5646 / BM123;
RX PubMed=15006821; DOI=10.1128/aem.70.3.1874-1881.2004;
RA He A., Li T., Daniels L., Fotheringham I., Rosazza J.P.;
RT "Nocardia sp. carboxylic acid reductase: cloning, expression, and
RT characterization of a new aldehyde oxidoreductase family.";
RL Appl. Environ. Microbiol. 70:1874-1881(2004).
RN [2]
RP PROTEIN SEQUENCE OF 2-17 AND 516-531, FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, KINETIC PARAMETERS, ACTIVITY REGULATION, AND
RP SUBUNIT.
RC STRAIN=DSM 45197 / JCM 18299 / NRRL 5646 / BM123;
RX PubMed=9171390; DOI=10.1128/jb.179.11.3482-3487.1997;
RA Li T., Rosazza J.P.;
RT "Purification, characterization, and properties of an aryl aldehyde
RT oxidoreductase from Nocardia sp. strain NRRL 5646.";
RL J. Bacteriol. 179:3482-3487(1997).
RN [3]
RP REACTION MECHANISM.
RC STRAIN=DSM 45197 / JCM 18299 / NRRL 5646 / BM123;
RX PubMed=9852085; DOI=10.1074/jbc.273.51.34230;
RA Li T., Rosazza J.P.;
RT "NMR identification of an acyl-adenylate intermediate in the aryl-aldehyde
RT oxidoreductase catalyzed reaction.";
RL J. Biol. Chem. 273:34230-34233(1998).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RA Venkitasubramanian P., Daniels L., Rosazza J.P.;
RT "Biocatalytic reduction of carboxylic acids.";
RL (In) Patel R. (eds.);
RL Biocatalysis in Pharmaceutical and Biotechnology Industries, pp.425-440,
RL CRC Press LLC, Boca Raton (2006).
RN [5]
RP FUNCTION, COFACTOR, PHOSPHOPANTETHEINYLATION AT SER-689, KINETIC
RP PARAMETERS, MUTAGENESIS OF SER-689, AND REACTION MECHANISM.
RC STRAIN=DSM 45197 / JCM 18299 / NRRL 5646 / BM123;
RX PubMed=17102130; DOI=10.1074/jbc.m607980200;
RA Venkitasubramanian P., Daniels L., Rosazza J.P.;
RT "Reduction of carboxylic acids by Nocardia aldehyde oxidoreductase requires
RT a phosphopantetheinylated enzyme.";
RL J. Biol. Chem. 282:478-485(2007).
RN [6] {ECO:0007744|PDB:5MSC, ECO:0007744|PDB:5MSD, ECO:0007744|PDB:5MSQ}
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) IN COMPLEXES WITH AMP AND BENZOIC
RP ACID, AND DOMAIN.
RX PubMed=28719588; DOI=10.1038/nchembio.2434;
RA Gahloth D., Dunstan M.S., Quaglia D., Klumbys E., Lockhart-Cairns M.P.,
RA Hill A.M., Derrington S.R., Scrutton N.S., Turner N.J., Leys D.;
RT "Structures of carboxylic acid reductase reveal domain dynamics underlying
RT catalysis.";
RL Nat. Chem. Biol. 13:975-981(2017).
CC -!- FUNCTION: Catalyzes the ATP- and NADPH-dependent reduction of
CC carboxylic acids to the corresponding aldehydes. Catalyzes the
CC reduction of a very wide range of aliphatic carboxylic acids as well as
CC many aryl carboxylic acids. Aryl carboxylic acid substrates include
CC substituted benzoic acids, phenyl-substituted aliphatic acids,
CC heterocyclic carboxylic acids, and polyaromatic ring carboxylic acids.
CC Cannot reduce benzaldehyde to benzyl alcohol.
CC {ECO:0000269|PubMed:15006821, ECO:0000269|PubMed:17102130,
CC ECO:0000269|PubMed:9171390, ECO:0000269|Ref.4}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a carboxylate + ATP + H(+) + NADPH = AMP + an aldehyde +
CC diphosphate + NADP(+); Xref=Rhea:RHEA:50916, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000255|HAMAP-Rule:MF_02247,
CC ECO:0000269|PubMed:15006821, ECO:0000269|PubMed:17102130,
CC ECO:0000269|PubMed:9171390, ECO:0000269|Ref.4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AMP + an aromatic aldehyde + diphosphate + NADP(+) = an
CC aromatic carboxylate + ATP + H(+) + NADPH; Xref=Rhea:RHEA:19229,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:33855, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:91007, ChEBI:CHEBI:456215; EC=1.2.1.30;
CC Evidence={ECO:0000269|PubMed:17102130, ECO:0000269|PubMed:9171390,
CC ECO:0000269|Ref.4};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02247,
CC ECO:0000269|PubMed:17102130};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255|HAMAP-
CC Rule:MF_02247, ECO:0000269|PubMed:17102130};
CC -!- ACTIVITY REGULATION: Is competitively inhibited by anthranilate when
CC using benzoate as substrate. {ECO:0000269|PubMed:9171390}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=645 uM for benzoate {ECO:0000269|PubMed:17102130,
CC ECO:0000269|PubMed:9171390};
CC KM=57.3 uM for ATP {ECO:0000269|PubMed:17102130,
CC ECO:0000269|PubMed:9171390};
CC KM=29.3 uM for NADPH {ECO:0000269|PubMed:17102130,
CC ECO:0000269|PubMed:9171390};
CC KM=34.5 uM for (R)-(-)-alpha-methyl-4-(2-methylpropyl)-benzeneacetate
CC ((R)-ibuprofen) {ECO:0000269|PubMed:17102130,
CC ECO:0000269|PubMed:9171390};
CC KM=155 uM for (S)-(+)-alpha-methyl-4-(2-methylpropyl)-benzeneacetate
CC ((S)-ibuprofen) {ECO:0000269|PubMed:17102130,
CC ECO:0000269|PubMed:9171390};
CC Vmax=0.902 umol/min/mg enzyme with benzoate as substrate
CC {ECO:0000269|PubMed:17102130, ECO:0000269|PubMed:9171390};
CC Vmax=1.33 umol/min/mg enzyme with (R)-(-)-alpha-methyl-4-(2-
CC methylpropyl)-benzeneacetate as substrate
CC {ECO:0000269|PubMed:17102130, ECO:0000269|PubMed:9171390};
CC Vmax=0.15 umol/min/mg enzyme with (S)-(+)-alpha-methyl-4-(2-
CC methylpropyl)-benzeneacetate as substrate
CC {ECO:0000269|PubMed:17102130, ECO:0000269|PubMed:9171390};
CC Note=Vmax is 3 times higher than that of the natural enzyme when
CC recombinant apo-Car is incubated with the purified PPTase Npt and
CC CoA. {ECO:0000269|PubMed:17102130};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:9171390}.
CC -!- DOMAIN: The N-terminal domain likely catalyzes substrate activation by
CC formation of an initial acyl-AMP intermediate, the central region
CC contains the phosphopantetheine attachment site, and the C-terminal
CC domain catalyzes the reduction by NADPH of the intermediate thioester
CC formed from the attack of the phosphopantetheine thiol at the carbonyl
CC carbon of acyl-AMP (PubMed:17102130). Large-scale domain motions occur
CC between the adenylation and thiolation states. Phosphopantetheine
CC binding alters the orientation of a key Asp, resulting in a productive
CC orientation of the bound nicotinamide. This ensures that further
CC reduction of the aldehyde product does not occur (PubMed:28719588).
CC {ECO:0000269|PubMed:17102130, ECO:0000269|PubMed:28719588}.
CC -!- PTM: 4'-phosphopantetheine is transferred from CoA to Ser-689 by Npt.
CC -!- MISCELLANEOUS: The conversion of carboxylic acid into aldehyde involves
CC three key steps: adenylation of the bound carboxylic acid substrate to
CC form an AMP-acyl intermediate, formation of a thioester linkage between
CC the acyl moiety and the phosphopantetheine prosthetic group, and
CC reduction of the thioester intermediate to the aldehyde.
CC {ECO:0000305|PubMed:17102130}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC Carboxylic acid reductase subfamily. {ECO:0000255|HAMAP-Rule:MF_02247,
CC ECO:0000305}.
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DR EMBL; AY495697; AAR91681.1; -; Genomic_DNA.
DR PDB; 5MSC; X-ray; 1.85 A; A=1-1174.
DR PDB; 5MSD; X-ray; 1.71 A; A=1-1174.
DR PDB; 5MSQ; X-ray; 1.74 A; A=1-1174.
DR PDBsum; 5MSC; -.
DR PDBsum; 5MSD; -.
DR PDBsum; 5MSQ; -.
DR AlphaFoldDB; Q6RKB1; -.
DR SMR; Q6RKB1; -.
DR KEGG; ag:AAR91681; -.
DR BioCyc; MetaCyc:MON-20627; -.
DR BRENDA; 1.2.1.30; 10331.
DR GO; GO:0047683; F:aryl-aldehyde dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR CDD; cd05235; SDR_e1; 1.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR HAMAP; MF_02247; Carbox_acid_reduct; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR046407; CAR.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Direct protein sequencing; NADP;
KW Nucleotide-binding; Oxidoreductase; Phosphopantetheine; Phosphoprotein.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9171390"
FT CHAIN 2..1174
FT /note="Carboxylic acid reductase"
FT /id="PRO_0000425449"
FT DOMAIN 655..730
FT /note="Carrier"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 300
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSC,
FT ECO:0007744|PDB:5MSD, ECO:0007744|PDB:5MSQ"
FT BINDING 395
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSC,
FT ECO:0007744|PDB:5MSD, ECO:0007744|PDB:5MSQ"
FT BINDING 416..417
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSC,
FT ECO:0007744|PDB:5MSD, ECO:0007744|PDB:5MSQ"
FT BINDING 421
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSD,
FT ECO:0007744|PDB:5MSQ"
FT BINDING 495
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSC,
FT ECO:0007744|PDB:5MSD, ECO:0007744|PDB:5MSQ"
FT BINDING 507..510
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSC,
FT ECO:0007744|PDB:5MSD, ECO:0007744|PDB:5MSQ"
FT BINDING 516
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 616
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSD,
FT ECO:0007744|PDB:5MSQ"
FT BINDING 787..790
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 814
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 824
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 880..882
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 920
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 956
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 960
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT BINDING 983
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT MOD_RES 689
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT ECO:0000269|PubMed:17102130"
FT MUTAGEN 689
FT /note="S->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:17102130"
FT HELIX 6..20
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 22..26
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 31..38
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 44..54
FT /evidence="ECO:0007829|PDB:5MSD"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 58..70
FT /evidence="ECO:0007829|PDB:5MSD"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 77..89
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 90..105
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 126..138
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 173..181
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 199..214
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 224..232
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 249..255
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 269..277
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 291..294
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 301..312
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 316..319
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 328..335
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 338..342
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 344..361
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 368..381
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 389..396
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 400..410
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 414..420
FT /evidence="ECO:0007829|PDB:5MSD"
FT TURN 421..423
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 424..429
FT /evidence="ECO:0007829|PDB:5MSD"
FT TURN 435..437
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 438..444
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 460..467
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 478..483
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 491..501
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 504..510
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 511..513
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 522..524
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 525..532
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 538..544
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 549..551
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 553..558
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 560..563
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 568..585
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:5MSD"
FT STRAND 595..599
FT /evidence="ECO:0007829|PDB:5MSD"
FT TURN 606..609
FT /evidence="ECO:0007829|PDB:5MSD"
FT HELIX 619..638
FT /evidence="ECO:0007829|PDB:5MSD"
SQ SEQUENCE 1174 AA; 128346 MW; D95F16957D6F95D8 CRC64;
MAVDSPDERL QRRIAQLFAE DEQVKAARPL EAVSAAVSAP GMRLAQIAAT VMAGYADRPA
AGQRAFELNT DDATGRTSLR LLPRFETITY RELWQRVGEV AAAWHHDPEN PLRAGDFVAL
LGFTSIDYAT LDLADIHLGA VTVPLQASAA VSQLIAILTE TSPRLLASTP EHLDAAVECL
LAGTTPERLV VFDYHPEDDD QRAAFESARR RLADAGSLVI VETLDAVRAR GRDLPAAPLF
VPDTDDDPLA LLIYTSGSTG TPKGAMYTNR LAATMWQGNS MLQGNSQRVG INLNYMPMSH
IAGRISLFGV LARGGTAYFA AKSDMSTLFE DIGLVRPTEI FFVPRVCDMV FQRYQSELDR
RSVAGADLDT LDREVKADLR QNYLGGRFLV AVVGSAPLAA EMKTFMESVL DLPLHDGYGS
TEAGASVLLD NQIQRPPVLD YKLVDVPELG YFRTDRPHPR GELLLKAETT IPGYYKRPEV
TAEIFDEDGF YKTGDIVAEL EHDRLVYVDR RNNVLKLSQG EFVTVAHLEA VFASSPLIRQ
IFIYGSSERS YLLAVIVPTD DALRGRDTAT LKSALAESIQ RIAKDANLQP YEIPRDFLIE
TEPFTIANGL LSGIAKLLRP NLKERYGAQL EQMYTDLATG QADELLALRR EAADLPVLET
VSRAAKAMLG VASADMRPDA HFTDLGGDSL SALSFSNLLH EIFGVEVPVG VVVSPANELR
DLANYIEAER NSGAKRPTFT SVHGGGSEIR AADLTLDKFI DARTLAAADS IPHAPVPAQT
VLLTGANGYL GRFLCLEWLE RLDKTGGTLI CVVRGSDAAA ARKRLDSAFD SGDPGLLEHY
QQLAARTLEV LAGDIGDPNL GLDDATWQRL AETVDLIVHP AALVNHVLPY TQLFGPNVVG
TAEIVRLAIT ARRKPVTYLS TVGVADQVDP AEYQEDSDVR EMSAVRVVRE SYANGYGNSK
WAGEVLLREA HDLCGLPVAV FRSDMILAHS RYAGQLNVQD VFTRLILSLV ATGIAPYSFY
RTDADGNRQR AHYDGLPADF TAAAITALGI QATEGFRTYD VLNPYDDGIS LDEFVDWLVE
SGHPIQRITD YSDWFHRFET AIRALPEKQR QASVLPLLDA YRNPCPAVRG AILPAKEFQA
AVQTAKIGPE QDIPHLSAPL IDKYVSDLEL LQLL
