ID HEM1_MANSM Reviewed; 444 AA. AC Q65SX9; DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 25-OCT-2004, 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}; OrderedLocusNames=MS1324; OS Mannheimia succiniciproducens (strain MBEL55E). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Pasteurellales; OC Pasteurellaceae; Basfia. OX NCBI_TaxID=221988; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=MBEL55E; RX PubMed=15378067; DOI=10.1038/nbt1010; RA Hong S.H., Kim J.S., Lee S.Y., In Y.H., Choi S.S., Rih J.-K., Kim C.H., RA Jeong H., Hur C.G., Kim J.J.; RT "The genome sequence of the capnophilic rumen bacterium Mannheimia RT succiniciproducens."; RL Nat. Biotechnol. 22:1275-1281(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; AE016827; AAU37931.1; -; Genomic_DNA. DR RefSeq; WP_011200498.1; NC_006300.1. DR AlphaFoldDB; Q65SX9; -. DR SMR; Q65SX9; -. DR STRING; 221988.MS1324; -. DR KEGG; msu:MS1324; -. DR eggNOG; COG0373; Bacteria. DR HOGENOM; CLU_035113_2_2_6; -. DR OrthoDB; 110209at2; -. DR UniPathway; UPA00251; UER00316. DR Proteomes; UP000000607; 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..444 FT /note="Glutamyl-tRNA reductase" FT /id="PRO_0000114038" 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 117 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 122..124 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 128 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 202..207 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT SITE 107 FT /note="Important for activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" SQ SEQUENCE 444 AA; 50410 MW; 758DB351D24DE442 CRC64; MTILVLGINH KTASVALREK VAFSPEKRDL AFQQIAQSEL AQSEVILSTC NRTEIYLHNK HISPEADQEN QRWLEQCIQW FADVHQLDVD ELRNCLYIKQ NQSAVNHLMR VSCGLDSLVL GEPQILGQVK QAYQYSEDYC QAQHMPMSSE FSRLFQKTFS VAKRVRTETN IGNSAVSVAY AACSLARQIF EGLKDLNILL VGAGETIELV ARHLLRHGVK KLMISNRTLA RAELLVEKLE HNKYIQVLSL QQLQDGLNQA DIVISSTGSP IVLITAEMVK QAQQKRRNAP MLIVDIAVPR DVDERVEKLD GVYHYTVDDL HSIIQRNLSE REKASKEAET IIDAEASDFF EWMKVHQFSN LIRTYRESAE QIRQDLLEKA VQAIGQNEDP ETVLQELSYK LMNKLIHSPT QAMQAMMKQG SIQGLRSFSS ALGIADKKER NPQK //