ID   HEM1_METFK              Reviewed;         414 AA.
AC   Q1GYE9;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 1.
DT   27-MAR-2024, entry version 106.
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=Mfla_2473;
OS   Methylobacillus flagellatus (strain KT / ATCC 51484 / DSM 6875).
OC   Bacteria; Pseudomonadota; Betaproteobacteria; Nitrosomonadales;
OC   Methylophilaceae; Methylobacillus.
OX   NCBI_TaxID=265072;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=KT / ATCC 51484 / DSM 6875;
RG   US DOE Joint Genome Institute;
RA   Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C.,
RA   Glavina del Rio T., Hammon N., Israni S., Dalin E., Tice H., Pitluck S.,
RA   Brettin T., Bruce D., Han C., Tapia R., Saunders E., Gilna P., Schmutz J.,
RA   Larimer F., Land M., Kyrpides N., Anderson I., Richardson P.;
RT   "Complete sequence of Methylobacillus flagellatus KT.";
RL   Submitted (MAR-2006) 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; CP000284; ABE50738.1; -; Genomic_DNA.
DR   RefSeq; WP_011480691.1; NC_007947.1.
DR   AlphaFoldDB; Q1GYE9; -.
DR   SMR; Q1GYE9; -.
DR   STRING; 265072.Mfla_2473; -.
DR   KEGG; mfa:Mfla_2473; -.
DR   eggNOG; COG0373; Bacteria.
DR   HOGENOM; CLU_035113_2_2_4; -.
DR   OrthoDB; 110209at2; -.
DR   UniPathway; UPA00251; UER00316.
DR   Proteomes; UP000002440; 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; Reference proteome.
FT   CHAIN           1..414
FT                   /note="Glutamyl-tRNA reductase"
FT                   /id="PRO_1000004638"
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         104
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         109..111
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         115
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         184..189
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   SITE            94
FT                   /note="Important for activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
SQ   SEQUENCE   414 AA;  45810 MW;  0C8AF430F0F13B0C CRC64;
     MHLFTVGVNH TTAPVSIREN VAFQNEHLSG ALRDLNSHGI REAAILSTCN RTELYCNTDD
     PQKALEWLAN YHRLKPQAIA PYMYTLPQEN AVKHAFRVAS GLDSMVLGEA QILGQMKQAV
     RIAENAGTLG TLLHKLFQRT FSVAKEVRTN TNIGANSVSL AAASTRLAQR IFGALNNQHV
     LFIGAGEMIE LCAEHFAAHR PLSLTVANRT LERGQELAAS IGGTSMLLAD LPDRLAEFDI
     VITSTASQLP IVGLGMVERA IRARKHKPMF MVDLAVPRDI EPEAGELDDV FLYTVDDLAQ
     IVQEGMENRQ EAAAEAEAII DMRVENFMQW LKTRSAVPTI RALREQAERH RLNELEKARK
     LLARGHDPAQ VLDALSNALT NKLLHGPSHA LNSATGEDRE QLEATLRQLY QIHH
//