ID   HEM1_METMA              Reviewed;         448 AA.
AC   Q8PW60;
DT   01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 148.
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=MM_1741;
OS   Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM
OS   11833 / OCM 88) (Methanosarcina frisia).
OC   Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia;
OC   Methanosarcinales; Methanosarcinaceae; Methanosarcina.
OX   NCBI_TaxID=192952;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88;
RX   PubMed=12125824;
RA   Deppenmeier U., Johann A., Hartsch T., Merkl R., Schmitz R.A.,
RA   Martinez-Arias R., Henne A., Wiezer A., Baeumer S., Jacobi C.,
RA   Brueggemann H., Lienard T., Christmann A., Boemecke M., Steckel S.,
RA   Bhattacharyya A., Lykidis A., Overbeek R., Klenk H.-P., Gunsalus R.P.,
RA   Fritz H.-J., Gottschalk G.;
RT   "The genome of Methanosarcina mazei: evidence for lateral gene transfer
RT   between Bacteria and Archaea.";
RL   J. Mol. Microbiol. Biotechnol. 4:453-461(2002).
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; AE008384; AAM31437.1; -; Genomic_DNA.
DR   RefSeq; WP_011033681.1; NC_003901.1.
DR   AlphaFoldDB; Q8PW60; -.
DR   SMR; Q8PW60; -.
DR   GeneID; 82160792; -.
DR   KEGG; mma:MM_1741; -.
DR   PATRIC; fig|192952.21.peg.2017; -.
DR   eggNOG; arCOG01036; Archaea.
DR   HOGENOM; CLU_035113_0_0_2; -.
DR   UniPathway; UPA00251; UER00316.
DR   Proteomes; UP000000595; 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; IPR018214; GluRdtase_CS.
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.
DR   PROSITE; PS00747; GLUTR; 1.
PE   3: Inferred from homology;
KW   NADP; Oxidoreductase; Porphyrin biosynthesis.
FT   CHAIN           1..448
FT                   /note="Glutamyl-tRNA reductase"
FT                   /id="PRO_0000114103"
FT   ACT_SITE        49
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         48..51
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         100
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         105..107
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         180..185
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   SITE            90
FT                   /note="Important for activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
SQ   SEQUENCE   448 AA;  50562 MW;  0733780153168AD9 CRC64;
     MTEISSMVIS HKKAKVEEME SAWHGDLDGL LRNLYKHEYV YECVVLKTCN RVEIYVVSPK
     SSSVLFSFAK EMGASTHIID FYGHDESLEH LLRLAGGLES MIVGEDQILG QIKDLYAYSK
     KAGTTGKILE TAFEKAIQVG KRIRNETRIN KGSVSIGSAA VDLAEDIFGG LTGKNVLVIG
     AGEIGVLVAK ALAEKDIEAI YIANRTYKKA EEIAYELGGH AVRLDDIRDY LPGADVVISG
     TGAPHYILTR EIVEEAIKCR ERKLLLIDIA NPRDIEESVV ELENVELCNI DNLRVISERT
     LRMRKEEAKK AEAIIQEEIR LLNLQYKRQK ADRLISELYK QVYDVRLRER QKAVNRLSSY
     HTIGDIETEV LDDLTRSIVN KILGEPTKVL RQAAELGNEE FLDVVSRVFC LDKEKVRFEK
     IKQAKFDQIK PGCTKEQAEV KEEYAVKD
//