ID   HEM1_MYCGI              Reviewed;         455 AA.
AC   A4T341;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-MAY-2007, sequence version 1.
DT   27-MAR-2024, entry version 111.
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=Mflv_0067;
OS   Mycolicibacterium gilvum (strain PYR-GCK) (Mycobacterium gilvum (strain
OS   PYR-GCK)).
OC   Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC   Mycolicibacterium.
OX   NCBI_TaxID=350054;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=PYR-GCK;
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., Kyrpides N., Mikhailova N., Miller C., Richardson P.;
RT   "Complete sequence of chromosome of Mycobacterium gilvum PYR-GCK.";
RL   Submitted (APR-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; CP000656; ABP42563.1; -; Genomic_DNA.
DR   AlphaFoldDB; A4T341; -.
DR   SMR; A4T341; -.
DR   STRING; 350054.Mflv_0067; -.
DR   KEGG; mgi:Mflv_0067; -.
DR   eggNOG; COG0373; Bacteria.
DR   HOGENOM; CLU_035113_4_0_11; -.
DR   OrthoDB; 110209at2; -.
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..455
FT                   /note="Glutamyl-tRNA reductase"
FT                   /id="PRO_1000075414"
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         109
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         114..116
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         120
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   BINDING         189..194
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT   SITE            99
FT                   /note="Important for activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
SQ   SEQUENCE   455 AA;  48012 MW;  C1E1BA66C43B8714 CRC64;
     MSVLLFGVSH RSAPVSVLEQ LSTDESDQAK IIAEVLRSSL VTEAMVLSTC NRVEIYAVVE
     AFHGGLSVIG QVLSDHSGMS LQDLTKYAYV RYAEAAVEHL FAVASGLDSA VVGEQQVLGQ
     VRRAYASAES NHTVGRTLHE LSQRALAVGK RVHSETGIDR AGASVVSVAL DVAEKKVGPL
     AGRSAVVVGA GSMGALAATQ LARAGIERIH VVNRSLPRGK RLAENIRGYG IAAEAYPFDH
     LPPLLTDADI VVSCTGAVRP VVSLADVHRG LAHVREPKDL VICDLGMPRD VDAAVAGLPG
     VFVIDMDRIL REPTAKTATS DADAARSIVA TEVANYLAGQ RVAEVTPTVT ALRQRAADVV
     EAELLRLDNR LPGLDSSHRD EVANTVRRVV DKLLHAPTVR VKQLASAPGG DSYAEALREL
     FELDQHAVDA VAGSELGAVS GDELAAPAID LDLTE
//