ID HEM1_MYCPA Reviewed; 459 AA. AC Q73SS1; DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, 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}; GN OrderedLocusNames=MAP_4002; OS Mycolicibacterium paratuberculosis (strain ATCC BAA-968 / K-10) OS (Mycobacterium paratuberculosis). OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae; OC Mycobacterium; Mycobacterium avium complex (MAC). OX NCBI_TaxID=262316; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-968 / K-10; RX PubMed=16116077; DOI=10.1073/pnas.0505662102; RA Li L., Bannantine J.P., Zhang Q., Amonsin A., May B.J., Alt D., Banerji N., RA Kanjilal S., Kapur V.; RT "The complete genome sequence of Mycobacterium avium subspecies RT paratuberculosis."; RL Proc. Natl. Acad. Sci. U.S.A. 102:12344-12349(2005). 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; AE016958; AAS06552.1; -; Genomic_DNA. DR RefSeq; WP_003879324.1; NZ_CP106873.1. DR AlphaFoldDB; Q73SS1; -. DR SMR; Q73SS1; -. DR STRING; 262316.MAP_4002; -. DR GeneID; 75272162; -. DR KEGG; mpa:MAP_4002; -. DR eggNOG; COG0373; Bacteria. DR HOGENOM; CLU_035113_2_2_11; -. DR UniPathway; UPA00251; UER00316. DR Proteomes; UP000000580; 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..459 FT /note="Glutamyl-tRNA reductase" FT /id="PRO_0000114041" 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 459 AA; 47934 MW; A4FC1D1FA5C3E05F CRC64; MSVLLFGVSH RSAPVSVLEQ LSIDESDHGK IVDRVLQSPL VTEAMVLSTC NRVEVYAVVD AFHGGLAVIG QVLSDHSGMS MSDLTKYAYV RYSEAAVEHL FAVASGLDSA VIGEQQVLGQ VRRAYATAET NRTVGRVLHE LAQRALSVGK RVHSETAIDA AGASVVSVAL DMADRRLGGL AGKTAVLVGA GAMGALAAAH LSRAGIGQVH VLNRSLSRAQ RLVRKIRETG VRADALPLEH LADALAGADV VVSCTGAVSP VVSLADVHHA LAAAGRSAAD ETAHPLVICD LGMPRDVDPA VAGLPGVWVV DVDRVQHEPS AHAAAADVDA ARTIVATEVA AYLAGQRMAE VTPTVTALRQ RAADVVEAEL LRLDNRLPGL DSAHREEVAR TVRRVVDKLL HAPTVRIKQL ASAPGGDSYA EALRELFELD QTAVDAVAAG ELPVIATGFD AGAPQQPTE //