ID HEM1_TROW8 Reviewed; 447 AA. AC Q83H91; DT 15-DEC-2003, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 27-MAR-2024, entry version 125. 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}; OrderedLocusNames=TW750; OS Tropheryma whipplei (strain TW08/27) (Whipple's bacillus). OC Bacteria; Actinomycetota; Actinomycetes; Micrococcales; Tropherymataceae; OC Tropheryma. OX NCBI_TaxID=218496; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=TW08/27; RX PubMed=12606174; DOI=10.1016/s0140-6736(03)12597-4; RA Bentley S.D., Maiwald M., Murphy L.D., Pallen M.J., Yeats C.A., Dover L.G., RA Norbertczak H.T., Besra G.S., Quail M.A., Harris D.E., von Herbay A., RA Goble A., Rutter S., Squares R., Squares S., Barrell B.G., Parkhill J., RA Relman D.A.; RT "Sequencing and analysis of the genome of the Whipple's disease bacterium RT Tropheryma whipplei."; RL Lancet 361:637-644(2003). 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; BX251412; CAD67409.1; -; Genomic_DNA. DR RefSeq; WP_011096687.1; NC_004551.1. DR AlphaFoldDB; Q83H91; -. DR SMR; Q83H91; -. DR GeneID; 67388531; -. DR KEGG; tws:TW750; -. DR HOGENOM; CLU_035113_4_1_11; -. 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 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 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..447 FT /note="Glutamyl-tRNA reductase" FT /id="PRO_0000114081" FT ACT_SITE 46 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 45..48 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 111 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 116..118 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 122 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 191..196 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT SITE 101 FT /note="Important for activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" SQ SEQUENCE 447 AA; 48838 MW; 7E5EF8E73584B2F1 CRC64; MLLCVSANHK KTSFTVLEQL ARVSPDFASE LVEAEDIDGA AILSTCNRFE VYIDAIQKGD QDDVCKTGLL VQNRIGELCN ISPSTIIEQT SFLAGCEVSR HLFSVATGLE SMIIGETEIA GQVKRALTYA QKCRTTSPEL ERLFQRASAV NRHIRQSTKI NEVGQSLVSL SLDLASSRIG DWSGVRAIIV GTGKYASKAL ALLKERGVVD ISVYSPSGHV NNICNTEGVR NIFNLQTALS GCDLVVGCSS VDKPVITKQD IETAQASGSR TSRVRPVGRP STDLTAIEAS NRSRHVLIDL GLPRNFDPAI SDLPTADLID LDMLRVHAPF DNLAAEKMAH ELAIESSSQF VNDCKQHEAT PVIVSFRNYL ESLTQTSLRR TDNCKHAQHA LKHFVNSLIH IPLTRCKQLA ANGESHKFAE SMEILFDVKT DCTEGTQYQS SCGKSFD //