ID HEM1_AKKM8 Reviewed; 340 AA. AC B2ULP2; DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-2008, sequence version 1. DT 27-MAR-2024, entry version 89. 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=Amuc_0091; OS Akkermansia muciniphila (strain ATCC BAA-835 / DSM 22959 / JCM 33894 / BCRC OS 81048 / CCUG 64013 / CIP 107961 / Muc). OC Bacteria; Verrucomicrobiota; Verrucomicrobiae; Verrucomicrobiales; OC Akkermansiaceae; Akkermansia. OX NCBI_TaxID=349741; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-835 / DSM 22959 / JCM 33894 / BCRC 81048 / CCUG 64013 RC / CIP 107961 / Muc; RX PubMed=21390229; DOI=10.1371/journal.pone.0016876; RA van Passel M.W., Kant R., Zoetendal E.G., Plugge C.M., Derrien M., RA Malfatti S.A., Chain P.S., Woyke T., Palva A., de Vos W.M., Smidt H.; RT "The genome of Akkermansia muciniphila, a dedicated intestinal mucin RT degrader, and its use in exploring intestinal metagenomes."; RL PLoS ONE 6:E16876-E16876(2011). 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; CP001071; ACD03936.1; -; Genomic_DNA. DR AlphaFoldDB; B2ULP2; -. DR SMR; B2ULP2; -. DR STRING; 349741.Amuc_0091; -. DR PaxDb; 349741-Amuc_0091; -. DR KEGG; amu:Amuc_0091; -. DR eggNOG; COG0373; Bacteria. DR HOGENOM; CLU_035113_3_0_0; -. DR OrthoDB; 110209at2; -. DR BioCyc; AMUC349741:G1GBX-112-MONOMER; -. DR UniPathway; UPA00251; UER00316. DR Proteomes; UP000001031; 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; IPR015895; 4pyrrol_synth_GluRdtase_N. 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; PF05201; GlutR_N; 1. DR Pfam; PF01488; Shikimate_DH; 1. DR SUPFAM; SSF69742; Glutamyl tRNA-reductase catalytic, N-terminal domain; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. PE 3: Inferred from homology; KW NADP; Oxidoreductase; Porphyrin biosynthesis; Reference proteome. FT CHAIN 1..340 FT /note="Glutamyl-tRNA reductase" FT /id="PRO_1000093112" 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 108 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 113..115 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 119 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT BINDING 188..193 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" FT SITE 98 FT /note="Important for activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087" SQ SEQUENCE 340 AA; 37606 MW; 27D3C2F5FF5D3612 CRC64; MRMVCLGLNH RTAPVEIRER FAVPSHKLRE EGQRIRSLPG VDQCVVLSTC NRMEIYYWSN APENAQEHIL SHFLGDGRGE LDMASYFYSH QGEDALGHLC RVLSGLDSMV LGETEIFGQV KTAYQTALDA GVTAACANKT FQKAFTIGKK VRTESQIHAG ATSVGSVAVE LAEQIFGDLS GTRVLILGAG EMSRVTGRAL HARGAEGIYV ANRSFDRAVE LAGMIGGQAI RYDVWGNYLR DIDVVVAATA APHCIITRET LLPLRASRKY RSLFLIDISV PRNISPDVAD IDEVYLYDID TLTQLADEAK RSRKQEVSRC EAIIRDSISR YFPDSALYDQ //