ID HEM1_NOCFA Reviewed; 477 AA. AC Q5YP69; DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 1. DT 27-MAR-2024, entry version 121. 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=NFA_51700; OS Nocardia farcinica (strain IFM 10152). OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Nocardiaceae; OC Nocardia. OX NCBI_TaxID=247156; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=IFM 10152; RX PubMed=15466710; DOI=10.1073/pnas.0406410101; RA Ishikawa J., Yamashita A., Mikami Y., Hoshino Y., Kurita H., Hotta K., RA Shiba T., Hattori M.; RT "The complete genomic sequence of Nocardia farcinica IFM 10152."; RL Proc. Natl. Acad. Sci. U.S.A. 101:14925-14930(2004). 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; AP006618; BAD60022.1; -; Genomic_DNA. DR RefSeq; WP_011211704.1; NC_006361.1. DR AlphaFoldDB; Q5YP69; -. DR SMR; Q5YP69; -. DR STRING; 247156.NFA_51700; -. DR GeneID; 61135748; -. DR KEGG; nfa:NFA_51700; -. DR eggNOG; COG0373; Bacteria. DR HOGENOM; CLU_035113_4_0_11; -. DR OrthoDB; 110209at2; -. DR UniPathway; UPA00251; UER00316. DR Proteomes; UP000006820; 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..477 FT /note="Glutamyl-tRNA reductase" FT /id="PRO_0000335054" 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 477 AA; 50016 MW; ECD6A35672A88F32 CRC64; MSVLLVGVSH RSAPVSVLEK VAITDADRPK LIDKMLASSH ISEAMIVSTC NRVEVYAVVD AFHGGLAEVG ELLTRHSGLA MPDLTKHAYV RYSEAAAEHL FAVASGLDSM VVGEQQVLSQ IRGAYATADA QQAVGRTLHE LAQHALRVGK RVHSETGIDR AGASVVSVAL DRAAQVLGDL AGRTAVVVGA GAMGGLSVAH LARAGIGRII VVNRTIERAR RLAETAASYG VESSALELDR LHEAMSAADV VLSCTGAVGA VVTLADTHRA LADRDRAEFP AGDRPLVFCD LGLPRDVEPA VAGLPGVAVI DIESLQRDPA AGAAADDTAA ARSIVAEELA KYLAGQRMAE VTPTVAALRQ RAAEVVEAEL LRLDSRLPGL AEPERDEVAR TVRRVVDKLL HAPTVRVKQL ASTPGGDSYA EALRELFELK PGAAQAVAAP MEITAIGPDR TAGLADDFTP GHRLDFEQHL GEEGKPA //