ID HEM1_THIDA Reviewed; 416 AA. AC Q3SG11; DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, 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=Tbd_2492; OS Thiobacillus denitrificans (strain ATCC 25259). OC Bacteria; Pseudomonadota; Betaproteobacteria; Nitrosomonadales; OC Thiobacillaceae; Thiobacillus. OX NCBI_TaxID=292415; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 25259; RX PubMed=16452431; DOI=10.1128/jb.188.4.1473-1488.2006; RA Beller H.R., Chain P.S., Letain T.E., Chakicherla A., Larimer F.W., RA Richardson P.M., Coleman M.A., Wood A.P., Kelly D.P.; RT "The genome sequence of the obligately chemolithoautotrophic, facultatively RT anaerobic bacterium Thiobacillus denitrificans."; RL J. Bacteriol. 188:1473-1488(2006). 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; CP000116; AAZ98445.1; -; Genomic_DNA. DR RefSeq; WP_011313004.1; NC_007404.1. DR AlphaFoldDB; Q3SG11; -. DR SMR; Q3SG11; -. DR STRING; 292415.Tbd_2492; -. DR KEGG; tbd:Tbd_2492; -. DR eggNOG; COG0373; Bacteria. DR HOGENOM; CLU_035113_2_2_4; -. DR OrthoDB; 110209at2; -. DR UniPathway; UPA00251; UER00316. DR Proteomes; UP000008291; 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..416 FT /note="Glutamyl-tRNA reductase" FT /id="PRO_0000335078" 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 105 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 110..112 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 116 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 185..190 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT SITE 95 FT /note="Important for activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" SQ SEQUENCE 416 AA; 45872 MW; 6ADDDBD3E9427BCA CRC64; MQLLTLGVNH HTAPLAIREQ VAFGPDKLVQ ALHELTLSKR ASEAAILSTC NRTELYVNTV SPDALSQWFA DFHHLDVREL APYLYTLPRE KAAQHAFRVA AGLDSMVLGE TQILGQMKQA VAAAEEAGTL GLLLHKLFQR TFSVAKEVRS STEIGANSVS MAAAAVRLAE RIFPSVKEQA CLFIGAGEMI ELCMTHFAAQ HPRRMTVANR TTERARPLAE RFNAGVIPLT ALPDEVAAYD IIITSTASPL PILGKGMLER AIRQRRHRPI FIVDLAVPRD VEAEVADMND VFLYSVDDLG QVVREGMDNR VAQVAQAEAI IETSVASFIH WMEGRELVPV IRGLRDAAER HRRHELDKAH KALARGDDPH AVLDAMSHGL ANKFLHAPTH GLSHATPEER AELVRLISQL YGLHPE //