HEMA_RUMJO
ID HEMA_RUMJO Reviewed; 515 AA.
AC Q59292;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Probable multifunctional siroheme biosynthesis protein HemA;
DE Includes:
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};
DE Includes:
DE RecName: Full=Precorrin-2 dehydrogenase;
DE EC=1.3.1.76;
DE Includes:
DE RecName: Full=Sirohydrochlorin ferrochelatase;
DE EC=4.99.1.4;
GN Name=hemA {ECO:0000255|HAMAP-Rule:MF_00087};
OS Ruminiclostridium josui (Clostridium josui).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Oscillospiraceae;
OC Ruminiclostridium.
OX NCBI_TaxID=1499;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=DSM 25723 / FERM P-9684 / JCM 17888 / KCTC 15379 / III;
RX PubMed=7665501; DOI=10.1128/jb.177.17.5169-5175.1995;
RA Fujino E., Fujino T., Karita S., Sakka K., Ohmiya K.;
RT "Cloning and sequencing of some genes responsible for porphyrin
RT biosynthesis from the anaerobic bacterium Clostridium josui.";
RL J. Bacteriol. 177:5169-5175(1995).
CC -!- FUNCTION: Multifunctional enzyme that catalyzes the NADPH-dependent
CC reduction of glutamyl-tRNA(Glu) to glutamate 1-semialdehyde (GSA), the
CC NAD-dependent ring dehydrogenation of precorrin-2 to sirohydrochlorin
CC and finally, the ferrochelation of sirohydrochlorin to yield siroheme.
CC {ECO:0000305|PubMed:7665501}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + precorrin-2 = 2 H(+) + NADH + sirohydrochlorin;
CC Xref=Rhea:RHEA:15613, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58351, ChEBI:CHEBI:58827; EC=1.3.1.76;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + siroheme = Fe(2+) + sirohydrochlorin;
CC Xref=Rhea:RHEA:24360, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:58351, ChEBI:CHEBI:60052; EC=4.99.1.4;
CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC sirohydrochlorin from precorrin-2: step 1/1.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; siroheme from sirohydrochlorin: step 1/1.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; sirohydrochlorin from precorrin-2: step 1/1.
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: In the N-terminal section; belongs to the glutamyl-tRNA
CC reductase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the precorrin-2
CC dehydrogenase / sirohydrochlorin ferrochelatase family. {ECO:0000305}.
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DR EMBL; D28503; BAA05860.1; -; Genomic_DNA.
DR PIR; I40809; I40809.
DR AlphaFoldDB; Q59292; -.
DR SMR; Q59292; -.
DR PRIDE; Q59292; -.
DR UniPathway; UPA00148; UER00222.
DR UniPathway; UPA00251; UER00316.
DR UniPathway; UPA00262; UER00222.
DR UniPathway; UPA00262; UER00376.
DR GO; GO:0008883; F:glutamyl-tRNA reductase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0051266; F:sirohydrochlorin ferrochelatase activity; IEA:UniProtKB-EC.
DR GO; GO:0009236; P:cobalamin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0019354; P:siroheme biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.460.30; -; 1.
DR HAMAP; MF_00087; Glu_tRNA_reductase; 1.
DR InterPro; IPR000343; 4pyrrol_synth_GluRdtase.
DR InterPro; IPR015895; 4pyrrol_synth_GluRdtase_N.
DR InterPro; IPR018214; GluRdtase_CS.
DR InterPro; IPR036343; GluRdtase_N_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR006151; Shikm_DH/Glu-tRNA_Rdtase.
DR InterPro; IPR006367; Sirohaem_synthase_N.
DR Pfam; PF05201; GlutR_N; 1.
DR Pfam; PF01488; Shikimate_DH; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF69742; SSF69742; 1.
DR TIGRFAMs; TIGR01470; cysG_Nterm; 1.
DR TIGRFAMs; TIGR01035; hemA; 1.
DR PROSITE; PS00747; GLUTR; 1.
PE 3: Inferred from homology;
KW Cobalamin biosynthesis; Lyase; Multifunctional enzyme; NAD; NADP;
KW Oxidoreductase; Porphyrin biosynthesis.
FT CHAIN 1..515
FT /note="Probable multifunctional siroheme biosynthesis
FT protein HemA"
FT /id="PRO_0000114012"
FT REGION 26..174
FT /note="Glutamyl-tRNA reductase"
FT REGION 367..507
FT /note="Precorrin-2 dehydrogenase /sirohydrochlorin
FT ferrochelatase"
FT ACT_SITE 69
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT BINDING 26..27
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 47..48
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 68..71
FT /ligand="L-glutamyl-tRNA(Glu)"
FT /ligand_id="ChEBI:CHEBI:29157"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="L-glutamyl-tRNA(Glu)"
FT /ligand_id="ChEBI:CHEBI:29157"
FT /evidence="ECO:0000250"
FT BINDING 132
FT /ligand="L-glutamyl-tRNA(Glu)"
FT /ligand_id="ChEBI:CHEBI:29157"
FT /evidence="ECO:0000250"
FT BINDING 138
FT /ligand="L-glutamyl-tRNA(Glu)"
FT /ligand_id="ChEBI:CHEBI:29157"
FT /evidence="ECO:0000250"
FT BINDING 206..211
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
FT SITE 117
FT /note="Important for activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00087"
SQ SEQUENCE 515 AA; 58368 MW; A9769824AA30DC4C CRC64;
MQLGRHNSGS IKKRLEMYIL SIISASLDYK SAAIDIRERF SYTSTRIREI LRRIKAADGV
SGAVLLCTCN RTELYISGDN IENMNPALLL CQLSGEEDHK SLMTLFSIRH DSEAIFHLME
VACGLQSMVL FEDRVITQVK NAAAISREEK TIDSTLETLF RLCITAAKKA KTEIKVKAVP
TSAAERAITE LSKKYCFTDK RILVIGNGEI GRLCCKKLIE LGAEITITLR KYKHGEIIIP
VGCNTIPYDE REEVLPLSDV VISATTSPHF TITYDMIEKL ERKPEIFVDL ALPRDIESSI
SNFTGVELYN LDRFYTDYSV LNQKEVSKIR EIINHFILQF EKWKDYREEA AFTKIPDLHN
DTLYGRFPLF IDLSGKKVLV VGGGEIATRR VKTLLRFGAD IYLVAPHLTS ELQEMLNCKL
INYREGYYES QDIQNMFLVI AATNDRETNH KVYLDAKEKG IQMSIADCRE ECSFYFPAIF
EFDGIVGGLV SQNGDNHSLV KSVAEQIRKI GQATD
