ID   HEM1_NATTJ              Reviewed;         458 AA.
AC   B2A1G4;
DT   24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   20-MAY-2008, sequence version 1.
DT   27-MAR-2024, entry version 88.
DE   RecName: Full=Glutamyl-tRNA reductase {ECO:0000255|HAMAP-Rule:MF_00087};
DE            Short=GluTR {ECO:0000255|HAMAP-Rule:MF_00087};
DE            EC=1.2.1.70 {ECO:0000255|HAMAP-Rule:MF_00087};
GN   Name=hemA {ECO:0000255|HAMAP-Rule:MF_00087};
GN   OrderedLocusNames=Nther_1121;
OS   Natranaerobius thermophilus (strain ATCC BAA-1301 / DSM 18059 /
OS   JW/NM-WN-LF).
OC   Bacteria; Bacillota; Clostridia; Natranaerobiales; Natranaerobiaceae;
OC   Natranaerobius.
OX   NCBI_TaxID=457570;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-1301 / DSM 18059 / JW/NM-WN-LF;
RG   US DOE Joint Genome Institute;
RA   Copeland A., Lucas S., Lapidus A., Glavina del Rio T., Dalin E., Tice H.,
RA   Bruce D., Goodwin L., Pitluck S., Chertkov O., Brettin T., Detter J.C.,
RA   Han C., Kuske C.R., Schmutz J., Larimer F., Land M., Hauser L.,
RA   Kyrpides N., Lykidis A., Mesbah N.M., Wiegel J.;
RT   "Complete sequence of chromosome of Natranaerobius thermophilus JW/NM-WN-
RT   LF.";
RL   Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the NADPH-dependent reduction of glutamyl-tRNA(Glu)
CC       to glutamate 1-semialdehyde (GSA). {ECO:0000255|HAMAP-Rule:MF_00087}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-4-amino-5-oxopentanoate + NADP(+) + tRNA(Glu) = H(+) + L-
CC         glutamyl-tRNA(Glu) + NADPH; Xref=Rhea:RHEA:12344, Rhea:RHEA-
CC         COMP:9663, Rhea:RHEA-COMP:9680, ChEBI:CHEBI:15378, ChEBI:CHEBI:57501,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78442,
CC         ChEBI:CHEBI:78520; EC=1.2.1.70; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_00087};
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; 5-aminolevulinate from L-glutamyl-tRNA(Glu): step 1/2.
CC       {ECO:0000255|HAMAP-Rule:MF_00087}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00087}.
CC   -!- DOMAIN: Possesses an unusual extended V-shaped dimeric structure with
CC       each monomer consisting of three distinct domains arranged along a
CC       curved 'spinal' alpha-helix. The N-terminal catalytic domain
CC       specifically recognizes the glutamate moiety of the substrate. The
CC       second domain is the NADPH-binding domain, and the third C-terminal
CC       domain is responsible for dimerization. {ECO:0000255|HAMAP-
CC       Rule:MF_00087}.
CC   -!- MISCELLANEOUS: During catalysis, the active site Cys acts as a
CC       nucleophile attacking the alpha-carbonyl group of tRNA-bound glutamate
CC       with the formation of a thioester intermediate between enzyme and
CC       glutamate, and the concomitant release of tRNA(Glu). The thioester
CC       intermediate is finally reduced by direct hydride transfer from NADPH,
CC       to form the product GSA. {ECO:0000255|HAMAP-Rule:MF_00087}.
CC   -!- SIMILARITY: Belongs to the glutamyl-tRNA reductase family.
CC       {ECO:0000255|HAMAP-Rule:MF_00087}.
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DR   EMBL; CP001034; ACB84704.1; -; Genomic_DNA.
DR   RefSeq; WP_012447579.1; NC_010718.1.
DR   AlphaFoldDB; B2A1G4; -.
DR   SMR; B2A1G4; -.
DR   STRING; 457570.Nther_1121; -.
DR   KEGG; nth:Nther_1121; -.
DR   eggNOG; COG0373; Bacteria.
DR   HOGENOM; CLU_035113_2_2_9; -.
DR   InParanoid; B2A1G4; -.
DR   OrthoDB; 110209at2; -.
DR   UniPathway; UPA00251; UER00316.
DR   Proteomes; UP000001683; Chromosome.
DR   GO; GO:0008883; F:glutamyl-tRNA reductase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd05213; NAD_bind_Glutamyl_tRNA_reduct; 1.
DR   Gene3D; 3.30.460.30; Glutamyl-tRNA reductase, N-terminal domain; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   HAMAP; MF_00087; Glu_tRNA_reductase; 1.
DR   InterPro; IPR000343; 4pyrrol_synth_GluRdtase.
DR   InterPro; IPR015896; 4pyrrol_synth_GluRdtase_dimer.
DR   InterPro; IPR015895; 4pyrrol_synth_GluRdtase_N.
DR   InterPro; IPR036453; GluRdtase_dimer_dom_sf.
DR   InterPro; IPR036343; GluRdtase_N_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR006151; Shikm_DH/Glu-tRNA_Rdtase.
DR   NCBIfam; TIGR01035; hemA; 1.
DR   PANTHER; PTHR43013; GLUTAMYL-TRNA REDUCTASE; 1.
DR   PANTHER; PTHR43013:SF1; GLUTAMYL-TRNA REDUCTASE; 1.
DR   Pfam; PF00745; GlutR_dimer; 1.
DR   Pfam; PF05201; GlutR_N; 1.
DR   Pfam; PF01488; Shikimate_DH; 1.
DR   PIRSF; PIRSF000445; 4pyrrol_synth_GluRdtase; 1.
DR   SUPFAM; SSF69742; Glutamyl tRNA-reductase catalytic, N-terminal domain; 1.
DR   SUPFAM; SSF69075; Glutamyl tRNA-reductase dimerization domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE   3: Inferred from homology;
KW   NADP; Oxidoreductase; Porphyrin biosynthesis; Reference proteome.
FT   CHAIN           1..458
FT                   /note="Glutamyl-tRNA reductase"
FT                   /id="PRO_1000093153"
FT   REGION          426..458
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        50
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         49..52
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         111
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         116..118
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         122
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         191..196
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   SITE            101
FT                   /note="Important for activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
SQ   SEQUENCE   458 AA;  51692 MW;  AE53385E112E0088 CRC64;
     MILAVIGINH ETASVETREQ LAFSSKQVKE LVQKLIEGQP IKEASVLSTC NRTEVHFTVN
     TGQIEAGKNH IMTYLSDFSD LDPREYVDHL YFITDQEAVS HIFKVTAGLN SLVTGETEIL
     GQVKKAYQLS DEAGGVDSIF HGLYQQALRT GKRVHRETGI NDNAASVSYA SVELATKIFG
     SLQNRRALII GAGKMSELAA RHLYSNGVKD VIVINRTIER AKNLADKFGG LYASYDQLSE
     WLNEIDIVIT STGAPHFVIK EEQIKRAMKS RKYSPMFLID IAVPRDVEPS VNNQDNAYLY
     TIDDLEAVVE SNMQERQEEA RNAELIISEE VAEFMVWYKT RDVVPLISAL REKAEDVRKM
     ELEKYHKKLK NLSPKEQEAV DKLTKSIVNK ILKEPVLRIK EFAVEDKSEL YMATLAQLFD
     LEDEVIPKDG EEHSSSKEVE SVTQSSTERG HHESDFHN
//