ID   HEM1_FRAP2              Reviewed;         414 AA.
AC   B0TX36;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   08-APR-2008, sequence version 1.
DT   27-MAR-2024, entry version 85.
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=Fphi_1071;
OS   Francisella philomiragia subsp. philomiragia (strain ATCC 25017 / FSC 153 /
OS   O#319-036).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Thiotrichales;
OC   Francisellaceae; Francisella.
OX   NCBI_TaxID=484022;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25017 / FSC 153 / O#319-036;
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   Chain P., Malfatti S., Shin M., Vergez L., Schmutz J., Larimer F., Land M.,
RA   Hauser L., Richardson P.;
RT   "Complete sequence of chromosome of Francisella philomiragia subsp.
RT   philomiragia ATCC 25017.";
RL   Submitted (DEC-2007) 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; CP000937; ABZ87294.1; -; Genomic_DNA.
DR   AlphaFoldDB; B0TX36; -.
DR   SMR; B0TX36; -.
DR   KEGG; fph:Fphi_1071; -.
DR   eggNOG; COG0373; Bacteria.
DR   HOGENOM; CLU_035113_2_2_6; -.
DR   UniPathway; UPA00251; UER00316.
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..414
FT                   /note="Glutamyl-tRNA reductase"
FT                   /id="PRO_1000075409"
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         108
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         113..115
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         119
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         188..193
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   SITE            98
FT                   /note="Important for activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
SQ   SEQUENCE   414 AA;  46658 MW;  AF19C2D4BB02FA0C CRC64;
     MALISLAIDY KKSPIEVRSE FALSGLDVSM LYKSILAIDN VVHAVILSTC NRTEVYLEIT
     DLRVVDDILA WWQSYVRNPE FKIRDYFKLR QGTEVIMHLM KLACGLESMV LGEPQILGQV
     KDSYTLSKKN HAIGKELDRV FQKVFATAKK VRSETRIGHC PVSVAFSAIT LAKKQLDNIS
     TKNVLIIGAG QTGELLFRHV TALNPKHIML ANRTIEKAEK ITSTFNNASA YYLSDLPKLI
     KKADIIIAAV NVTEYIVKCE DVGEKSRVFI DISIPQALDP KLGDLEQNAY YCVDDINTVI
     EGNKDKRKHE SSRAQKIIVK SLEDYLEKEK AIISNSAIKE LFQKADGLVD LSLEKSLAKI
     RNGKDPEEVL KRFAYEIKKK VLHYPVVGMK EASKQGRSDC LVCMKRMFGL NVEK
//