ID HEM1_THEM4 Reviewed; 368 AA. AC A6LKW9; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2007, sequence version 1. DT 27-MAR-2024, entry version 113. 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=Tmel_0706; OS Thermosipho melanesiensis (strain DSM 12029 / CIP 104789 / BI429). OC Bacteria; Thermotogota; Thermotogae; Thermotogales; Fervidobacteriaceae; OC Thermosipho. OX NCBI_TaxID=391009; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=DSM 12029 / CIP 104789 / BI429; RG US DOE Joint Genome Institute; RA Copeland A., Lucas S., Lapidus A., Barry K., Glavina del Rio T., Dalin E., RA Tice H., Pitluck S., Chertkov O., Brettin T., Bruce D., Detter J.C., RA Han C., Schmutz J., Larimer F., Land M., Hauser L., Kyrpides N., RA Mikhailova N., Nelson K., Gogarten J.P., Noll K., Richardson P.; RT "Complete sequence of Thermosipho melanesiensis BI429."; RL Submitted (MAY-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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP000716; ABR30570.1; -; Genomic_DNA. DR RefSeq; WP_012056931.1; NC_009616.1. DR AlphaFoldDB; A6LKW9; -. DR SMR; A6LKW9; -. DR STRING; 391009.Tmel_0706; -. DR KEGG; tme:Tmel_0706; -. DR eggNOG; COG0373; Bacteria. DR HOGENOM; CLU_035113_2_2_0; -. DR OrthoDB; 110209at2; -. DR UniPathway; UPA00251; UER00316. DR Proteomes; UP000001110; 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..368 FT /note="Glutamyl-tRNA reductase" FT /id="PRO_1000004716" FT ACT_SITE 44 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 43..46 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 89 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 94..96 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 164..169 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT SITE 79 FT /note="Important for activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" SQ SEQUENCE 368 AA; 42784 MW; 6074AC5A541663BC CRC64; MKLNLVGLGR NTPIYILEKF DFDEQEFFSS LKVKTTEVAV LKTCHRREIY YIGDKEPLTI NEIIEPYIIR KSGIDVVRHL FKVSCGLDSM VLGEHQILSQ VKNTHKNFCH GKILNKLFNE AVSLGKEART KTGINKYPLS ISYIAVKLIE EQINIEGKKI FVIGTGMMGQ KVIKYLVSRG ADIYISNRTI KKAYEIKKMF SEVNIVDFEE KYKHISSSDV VISATNAPHY VVEEKKVNSQ KNIIFIDLSM PRNIEPSIKE YHTLYTLEDL NEISKKYNKL RQEKISTIQN LIETRIKKFL TWYKLQTVKD DILYIQNLAE KLVYEEIEKL SKKILLDDNS LKQIQKSLKS CTKKIVSYHI NYIKEKVI //