ID   HEM1_METLZ              Reviewed;         424 AA.
AC   A2SQU1;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   27-MAR-2024, entry version 100.
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=Mlab_0523;
OS   Methanocorpusculum labreanum (strain ATCC 43576 / DSM 4855 / Z).
OC   Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia;
OC   Methanomicrobiales; Methanocorpusculaceae; Methanocorpusculum.
OX   NCBI_TaxID=410358;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43576 / DSM 4855 / Z;
RX   PubMed=21304657; DOI=10.4056/sigs.35575;
RA   Anderson I.J., Sieprawska-Lupa M., Goltsman E., Lapidus A., Copeland A.,
RA   Glavina Del Rio T., Tice H., Dalin E., Barry K., Pitluck S., Hauser L.,
RA   Land M., Lucas S., Richardson P., Whitman W.B., Kyrpides N.C.;
RT   "Complete genome sequence of Methanocorpusculum labreanum type strain Z.";
RL   Stand. Genomic Sci. 1:197-203(2009).
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; CP000559; ABN06697.1; -; Genomic_DNA.
DR   RefSeq; WP_011832898.1; NC_008942.1.
DR   AlphaFoldDB; A2SQU1; -.
DR   SMR; A2SQU1; -.
DR   STRING; 410358.Mlab_0523; -.
DR   GeneID; 4795403; -.
DR   KEGG; mla:Mlab_0523; -.
DR   eggNOG; arCOG01036; Archaea.
DR   HOGENOM; CLU_035113_0_0_2; -.
DR   OrthoDB; 4562at2157; -.
DR   UniPathway; UPA00251; UER00316.
DR   Proteomes; UP000000365; 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..424
FT                   /note="Glutamyl-tRNA reductase"
FT                   /id="PRO_0000335091"
FT   ACT_SITE        52
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         51..54
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         99
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         104..106
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         110
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         179..184
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   SITE            89
FT                   /note="Important for activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
SQ   SEQUENCE   424 AA;  46697 MW;  E4D07EF8F46E4DCB CRC64;
     MTRTLLTDIA VATADHSKYG EEVLGLFRFK DETAFFEKAS KIFPGVVLLE TCNRVEILVH
     GSAKQLRDFL HGEQRFGFDI LEGEAALMHL LELAAGTKSM IIGEDQILGQ MRRALLLAES
     HDTNDVITDV CLNTAIREGV SIRQKTSINK GAVSIGSAAV LLAEELMGDL DGKNILVVGG
     GEMGTLVARA LCEKNLRAIY VTNRSFDRAV LLAEEIKGRA MRLDQLYPCI ALSDVVISCT
     GAPHLIIHAD ELAETMNERF WPLDLEPRHL LLIDIAQPRD IDDACRDVPG VSLKTLDDLK
     SISEKNLAAR KTECEHADVL VKAALPEFIK AFNRAASGDL TKNLYTWAEE IRQREKNKAL
     SRLRDADPYL ESVIDDLTSA LTKKLLEDAA KSIRASAECT DTQTAEILLK AIISGEVSCI
     RRSE
//