LYSY_THET2
ID LYSY_THET2 Reviewed; 344 AA.
AC O50146; Q9ZND6;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=[LysW]-L-2-aminoadipate 6-phosphate reductase {ECO:0000255|HAMAP-Rule:MF_02083, ECO:0000305};
DE EC=1.2.1.103 {ECO:0000255|HAMAP-Rule:MF_02083, ECO:0000269|PubMed:26966182, ECO:0000305|PubMed:19620981};
GN Name=lysY {ECO:0000255|HAMAP-Rule:MF_02083, ECO:0000303|PubMed:19620981};
GN Synonyms=argC {ECO:0000303|PubMed:10074061, ECO:0000303|PubMed:9418242};
GN OrderedLocusNames=TT_C1542;
OS Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27).
OC Bacteria; Deinococcus-Thermus; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=262724;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-163 / DSM 7039 / HB27;
RX PubMed=15064768; DOI=10.1038/nbt956;
RA Henne A., Brueggemann H., Raasch C., Wiezer A., Hartsch T., Liesegang H.,
RA Johann A., Lienard T., Gohl O., Martinez-Arias R., Jacobi C.,
RA Starkuviene V., Schlenczeck S., Dencker S., Huber R., Klenk H.-P.,
RA Kramer W., Merkl R., Gottschalk G., Fritz H.-J.;
RT "The genome sequence of the extreme thermophile Thermus thermophilus.";
RL Nat. Biotechnol. 22:547-553(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-236.
RX PubMed=10074061; DOI=10.1128/jb.181.6.1713-1718.1999;
RA Kobashi N., Nishiyama M., Tanokura M.;
RT "Aspartate kinase-independent lysine synthesis in an extremely thermophilic
RT bacterium, Thermus thermophilus: lysine is synthesized via alpha-
RT aminoadipic acid not via diaminopimelic acid.";
RL J. Bacteriol. 181:1713-1718(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-344.
RC STRAIN=ATCC BAA-163 / DSM 7039 / HB27;
RX PubMed=9418242; DOI=10.1111/j.1574-6968.1997.tb12755.x;
RA Kosuge T., Hoshino T.;
RT "Molecular cloning and sequence analysis of the lysR gene from the
RT extremely thermophilic eubacterium, Thermus thermophilus HB27.";
RL FEMS Microbiol. Lett. 157:73-79(1997).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=ATCC BAA-163 / DSM 7039 / HB27;
RX PubMed=19620981; DOI=10.1038/nchembio.198;
RA Horie A., Tomita T., Saiki A., Kono H., Taka H., Mineki R., Fujimura T.,
RA Nishiyama C., Kuzuyama T., Nishiyama M.;
RT "Discovery of proteinaceous N-modification in lysine biosynthesis of
RT Thermus thermophilus.";
RL Nat. Chem. Biol. 5:673-679(2009).
RN [5] {ECO:0007744|PDB:5EIN, ECO:0007744|PDB:5EIO}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH LYSW-AASA AND NADP
RP AND OF MUTANT ALA-148 IN COMPLEX WITH SUBSTRATE ANALOG AND NADP, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, INTERACTION
RP WITH LYSW, AND MUTAGENESIS OF ARG-102; CYS-148; ARG-195; HIS-209; ARG-258;
RP LYS-271 AND ARG-278.
RC STRAIN=ATCC BAA-163 / DSM 7039 / HB27;
RX PubMed=26966182; DOI=10.1074/jbc.m115.707034;
RA Shimizu T., Tomita T., Kuzuyama T., Nishiyama M.;
RT "Crystal structure of the LysYLysW complex from Thermus thermophilus.";
RL J. Biol. Chem. 291:9948-9959(2016).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of [LysW]-
CC aminoadipate 6-phosphate to yield [LysW]-aminoadipate 6-semialdehyde.
CC {ECO:0000255|HAMAP-Rule:MF_02083, ECO:0000269|PubMed:26966182,
CC ECO:0000305|PubMed:19620981}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[amino-group carrier protein]-C-terminal-N-(1-carboxy-5-
CC oxopentan-1-yl)-L-glutamine + NADP(+) + phosphate = [amino-group
CC carrier protein]-C-terminal-N-(1-carboxy-5-phosphooxy-5-oxopentan-1-
CC yl)-L-glutamine + H(+) + NADPH; Xref=Rhea:RHEA:41948, Rhea:RHEA-
CC COMP:9712, Rhea:RHEA-COMP:9714, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78499,
CC ChEBI:CHEBI:78501; EC=1.2.1.103; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_02083, ECO:0000269|PubMed:26966182,
CC ECO:0000305|PubMed:19620981};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.8 uM for [LysW]-aminoadipate 6-semialdehyde
CC {ECO:0000269|PubMed:26966182};
CC KM=14 uM for NADP(+) {ECO:0000269|PubMed:26966182};
CC KM=12000 uM for phosphate {ECO:0000269|PubMed:26966182};
CC Note=kcat is 0.96 sec(-1). {ECO:0000269|PubMed:26966182};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-lysine from L-alpha-aminoadipate (Thermus route): step 3/5.
CC {ECO:0000255|HAMAP-Rule:MF_02083, ECO:0000269|PubMed:19620981}.
CC -!- SUBUNIT: Homotetramer (PubMed:26966182). Interacts with LysW. May form
CC a ternary complex with LysW and LysZ (PubMed:26966182).
CC {ECO:0000269|PubMed:26966182}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_02083}.
CC -!- SIMILARITY: Belongs to the NAGSA dehydrogenase family. Type 1
CC subfamily. LysY sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_02083,
CC ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA23878.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AE017221; AAS81884.1; -; Genomic_DNA.
DR EMBL; AB017109; BAA74767.1; -; mRNA.
DR EMBL; AB006681; BAA23878.1; ALT_INIT; Genomic_DNA.
DR PIR; T43947; T43947.
DR RefSeq; WP_011173916.1; NC_005835.1.
DR PDB; 5EIN; X-ray; 1.70 A; A/B=1-344.
DR PDB; 5EIO; X-ray; 1.80 A; A/B=1-344.
DR PDBsum; 5EIN; -.
DR PDBsum; 5EIO; -.
DR AlphaFoldDB; O50146; -.
DR SMR; O50146; -.
DR STRING; 262724.TT_C1542; -.
DR EnsemblBacteria; AAS81884; AAS81884; TT_C1542.
DR KEGG; tth:TT_C1542; -.
DR eggNOG; COG0002; Bacteria.
DR HOGENOM; CLU_006384_0_1_0; -.
DR OMA; FSWRNNN; -.
DR OrthoDB; 951261at2; -.
DR BioCyc; MetaCyc:MON-6802; -.
DR BRENDA; 1.2.1.103; 2305.
DR BRENDA; 1.2.1.106; 2305.
DR UniPathway; UPA00033; UER00037.
DR Proteomes; UP000000592; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043870; F:N-acetyl-gamma-aminoadipyl-phosphate reductase activity; IEA:RHEA.
DR GO; GO:0003942; F:N-acetyl-gamma-glutamyl-phosphate reductase activity; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0006526; P:arginine biosynthetic process; IEA:InterPro.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniRule.
DR HAMAP; MF_00150; ArgC_type1; 1.
DR HAMAP; MF_02083; LysY; 1.
DR InterPro; IPR023013; AGPR_AS.
DR InterPro; IPR000706; AGPR_type-1.
DR InterPro; IPR037535; LysY.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR000534; Semialdehyde_DH_NAD-bd.
DR InterPro; IPR012280; Semialdhyde_DH_dimer_dom.
DR Pfam; PF01118; Semialdhyde_dh; 1.
DR Pfam; PF02774; Semialdhyde_dhC; 1.
DR SMART; SM00859; Semialdhyde_dh; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01850; argC; 1.
DR PROSITE; PS01224; ARGC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Cytoplasm; Lysine biosynthesis;
KW NADP; Oxidoreductase.
FT CHAIN 1..344
FT /note="[LysW]-L-2-aminoadipate 6-phosphate reductase"
FT /id="PRO_0000112501"
FT ACT_SITE 148
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02083,
FT ECO:0000305|PubMed:26966182"
FT BINDING 12..15
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02083,
FT ECO:0000269|PubMed:26966182"
FT BINDING 36..38
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02083,
FT ECO:0000269|PubMed:26966182"
FT BINDING 75
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26966182"
FT BINDING 180
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26966182"
FT BINDING 184
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26966182"
FT BINDING 312
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02083,
FT ECO:0000269|PubMed:26966182"
FT MUTAGEN 102
FT /note="R->A: Strong decrease in activity."
FT /evidence="ECO:0000269|PubMed:26966182"
FT MUTAGEN 148
FT /note="C->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:26966182"
FT MUTAGEN 195
FT /note="R->A: 5-fold decrease in kcat and 40-fold increase
FT in Km for [LysW]-aminoadipate 6-semialdehyde."
FT /evidence="ECO:0000269|PubMed:26966182"
FT MUTAGEN 209
FT /note="H->A: Does not affect activity under basic
FT conditions. Strong decrease of activity under neutral
FT conditions."
FT /evidence="ECO:0000269|PubMed:26966182"
FT MUTAGEN 258
FT /note="R->A: Slight decrease in kcat and 17-fold increase
FT in Km for [LysW]-aminoadipate 6-semialdehyde."
FT /evidence="ECO:0000269|PubMed:26966182"
FT MUTAGEN 271
FT /note="K->A: 5-fold decrease in kcat and 70-fold increase
FT in Km for [LysW]-aminoadipate 6-semialdehyde."
FT /evidence="ECO:0000269|PubMed:26966182"
FT MUTAGEN 278
FT /note="R->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:26966182"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 29..35
FT /evidence="ECO:0007829|PDB:5EIN"
FT TURN 38..41
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:5EIN"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 84..88
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:5EIN"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 106..113
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:5EIO"
FT HELIX 130..137
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 148..163
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 171..177
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 179..182
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 192..195
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 200..205
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 210..215
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 236..244
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 250..261
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 291..297
FT /evidence="ECO:0007829|PDB:5EIN"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:5EIN"
FT STRAND 303..310
FT /evidence="ECO:0007829|PDB:5EIN"
FT TURN 312..317
FT /evidence="ECO:0007829|PDB:5EIN"
FT HELIX 318..329
FT /evidence="ECO:0007829|PDB:5EIN"
FT TURN 333..336
FT /evidence="ECO:0007829|PDB:5EIN"
SQ SEQUENCE 344 AA; 38051 MW; B11CE66CB2F04C15 CRC64;
MDKKTLSIVG ASGYAGGEFL RLALSHPYLE VKQVTSRRFA GEPVHFVHPN LRGRTNLKFI
PPEKLEPADI LVLALPHGVF AREFDRYSAL APILIDLSAD FRLKDPELYR RYYGEHPRPD
LLGCFVYAVP ELYREALKGA DWIAGAGCNA TATLLGLYPL LKAGVLKPTP IFVTLLISTS
AAGAEASPAS HHPERAGSIR VYKPTGHRHT AEVVENLPGR PEVHLTAIAT DRVRGILMTA
QCFVQDGWSE RDVWQAYREA YAGEPFIRLV KQKKGVHRYP DPRFVQGTNY ADIGFELEED
TGRLVVMTAI DNLVKGTAGH ALQALNVRMG WPETLGLDFP GLHP
