MOAA_STAA8
ID MOAA_STAA8 Reviewed; 340 AA.
AC P69848; Q2FVY5;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=GTP 3',8-cyclase {ECO:0000303|PubMed:25697423};
DE EC=4.1.99.22 {ECO:0000269|PubMed:23627491};
DE AltName: Full=Molybdenum cofactor biosynthesis protein A;
GN Name=moaA; OrderedLocusNames=SAOUHSC_02536;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
RP EPR SPECTROSCOPY, AND SUBSTRATE BINDING.
RX PubMed=19566093; DOI=10.1021/ja903978u;
RA Lees N.S., Haenzelmann P., Hernandez H.L., Subramanian S., Schindelin H.,
RA Johnson M.K., Hoffman B.M.;
RT "ENDOR spectroscopy shows that guanine N1 binds to [4Fe-4S] cluster II of
RT the S-adenosylmethionine-dependent enzyme MoaA: mechanistic implications.";
RL J. Am. Chem. Soc. 131:9184-9185(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP ASP-198; 330-ARG--LYS-332; GLY-339 AND GLY-340, AND REACTION MECHANISM.
RX PubMed=23627491; DOI=10.1021/ja401781t;
RA Hover B.M., Loksztejn A., Ribeiro A.A., Yokoyama K.;
RT "Identification of a cyclic nucleotide as a cryptic intermediate in
RT molybdenum cofactor biosynthesis.";
RL J. Am. Chem. Soc. 135:7019-7032(2013).
RN [4]
RP FUNCTION OF C-TERMINUS, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND REACTION MECHANISM.
RX PubMed=25697423; DOI=10.1021/ja512997j;
RA Hover B.M., Yokoyama K.;
RT "C-Terminal glycine-gated radical initiation by GTP 3',8-cyclase in the
RT molybdenum cofactor biosynthesis.";
RL J. Am. Chem. Soc. 137:3352-3359(2015).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF APOPROTEIN AND OF COMPLEX WITH
RP 4FE-4S AND S-ADENOSYL-L-METHIONINE, SUBUNIT, AND COFACTOR.
RC STRAIN=ATCC 35556 / SA113;
RX PubMed=15317939; DOI=10.1073/pnas.0404624101;
RA Haenzelmann P., Schindelin H.;
RT "Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and
RT its implications for molybdenum cofactor deficiency in humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12870-12875(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF WILD-TYPE AND MUTANT
RP ALA-17/ALA-266/ALA-268 IN COMPLEX WITH 5'-GTP; 4FE-4S AND
RP S-ADENOSYL-L-METHIONINE, AND MUTAGENESIS OF ARG-17; CYS-24; CYS-28; TYR-30;
RP CYS-31; LYS-69; ARG-71; THR-73; SER-126; ARG-192; PHE-260; ARG-266 AND
RP ARG-268.
RC STRAIN=ATCC 35556 / SA113;
RX PubMed=16632608; DOI=10.1073/pnas.0510711103;
RA Haenzelmann P., Schindelin H.;
RT "Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-
RT adenosylmethionine enzyme MoaA provides insights into its mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6829-6834(2006).
CC -!- FUNCTION: Catalyzes the cyclization of GTP to (8S)-3',8-cyclo-7,8-
CC dihydroguanosine 5'-triphosphate. {ECO:0000269|PubMed:23627491,
CC ECO:0000269|PubMed:25697423}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + GTP + S-adenosyl-L-methionine = (8S)-3',8-cyclo-7,8-
CC dihydroguanosine 5'-triphosphate + 5'-deoxyadenosine + A + H(+) + L-
CC methionine; Xref=Rhea:RHEA:49576, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17319, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:57844, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:131766; EC=4.1.99.22;
CC Evidence={ECO:0000269|PubMed:23627491, ECO:0000269|PubMed:25697423};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:15317939};
CC Note=Binds 2 [4Fe-4S] clusters. Binds 1 [4Fe-4S] cluster coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine and 1
CC [4Fe-4S] cluster coordinated with 3 cysteines and the GTP-derived
CC substrate. {ECO:0000269|PubMed:15317939};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.4 uM for GTP {ECO:0000269|PubMed:23627491};
CC KM=3.1 uM for GTP {ECO:0000269|PubMed:25697423};
CC KM=4.1 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:23627491};
CC KM=5.1 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:25697423};
CC Note=kcat is 0.045 min(-1). {ECO:0000269|PubMed:23627491,
CC ECO:0000269|PubMed:25697423};
CC -!- PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_01225}.
CC -!- SUBUNIT: Monomer and homodimer. {ECO:0000269|PubMed:15317939,
CC ECO:0000269|PubMed:16632608}.
CC -!- DOMAIN: The central core of the structure is composed of a partial TIM-
CC barrel fold deviating from the canonical TIM-barrel topology.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. MoaA family.
CC {ECO:0000255|HAMAP-Rule:MF_01225}.
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DR EMBL; CP000253; ABD31551.1; -; Genomic_DNA.
DR RefSeq; WP_000230173.1; NZ_LS483365.1.
DR RefSeq; YP_501000.1; NC_007795.1.
DR PDB; 1TV7; X-ray; 2.80 A; A/B=1-340.
DR PDB; 1TV8; X-ray; 2.20 A; A/B=1-340.
DR PDB; 2FB2; X-ray; 2.25 A; A/B=1-340.
DR PDB; 2FB3; X-ray; 2.35 A; A/B=1-340.
DR PDBsum; 1TV7; -.
DR PDBsum; 1TV8; -.
DR PDBsum; 2FB2; -.
DR PDBsum; 2FB3; -.
DR AlphaFoldDB; P69848; -.
DR SMR; P69848; -.
DR STRING; 1280.SAXN108_2517; -.
DR EnsemblBacteria; ABD31551; ABD31551; SAOUHSC_02536.
DR GeneID; 3921126; -.
DR KEGG; sao:SAOUHSC_02536; -.
DR PATRIC; fig|93061.5.peg.2287; -.
DR eggNOG; COG2896; Bacteria.
DR HOGENOM; CLU_009273_0_1_9; -.
DR OMA; IEFMPIG; -.
DR BRENDA; 4.1.99.22; 3352.
DR UniPathway; UPA00344; -.
DR EvolutionaryTrace; P69848; -.
DR PRO; PR:P69848; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0019008; C:molybdopterin synthase complex; IEA:InterPro.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule.
DR GO; GO:0061799; F:cyclic pyranopterin monophosphate synthase activity; IBA:GO_Central.
DR GO; GO:0061798; F:GTP 3',8'-cyclase activity; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_01225_B; MoaA_B; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR013483; MoaA.
DR InterPro; IPR000385; MoaA_NifB_PqqE_Fe-S-bd_CS.
DR InterPro; IPR010505; Mob_synth_C.
DR InterPro; IPR007197; rSAM.
DR Pfam; PF06463; Mob_synth_C; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR SMART; SM00729; Elp3; 1.
DR TIGRFAMs; TIGR02666; moaA; 1.
DR PROSITE; PS01305; MOAA_NIFB_PQQE; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; GTP-binding; Iron; Iron-sulfur; Lyase; Metal-binding;
KW Molybdenum cofactor biosynthesis; Nucleotide-binding; Reference proteome;
KW S-adenosyl-L-methionine.
FT CHAIN 1..340
FT /note="GTP 3',8-cyclase"
FT /id="PRO_0000152995"
FT DOMAIN 8..227
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT BINDING 17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 24
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 28
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 30
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 31
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 71
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 75
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 102
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 126
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 163
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 197
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 261
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 264
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 266..268
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT BINDING 278
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000269|PubMed:16632608,
FT ECO:0007744|PDB:2FB3"
FT MUTAGEN 17
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 24
FT /note="C->A: Loss of activity; when associated with A-28
FT and A-31."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 28
FT /note="C->A: Loss of activity; when associated with A-24
FT and A-31."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 30
FT /note="Y->A: Reduces activity by over 80%."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 31
FT /note="C->A: Loss of activity; when associated with A-24
FT and A-28."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 69
FT /note="K->A: Reduces activity by about 60%."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 71
FT /note="R->A: Strongly reduced affinity for GTP. Reduces
FT activity by about 80%."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 73
FT /note="T->A: Reduces activity by over 80%."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 126
FT /note="S->A: Reduces activity by over 80%."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 192
FT /note="R->A: Reduces activity by about 80%."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 198
FT /note="D->A: Loss of activity by 92%."
FT /evidence="ECO:0000269|PubMed:25697423"
FT MUTAGEN 260
FT /note="F->A: Alters stability of FeS cluster and alters
FT protein stability."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 260
FT /note="F->L: Reduces activity by about 80%."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 266
FT /note="R->A: Loss of activity. Strongly reduced affinity
FT for GTP."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 268
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16632608"
FT MUTAGEN 330..332
FT /note="RKK->AAA: Loss of activity by 92%."
FT /evidence="ECO:0000269|PubMed:25697423"
FT MUTAGEN 339
FT /note="G->A,S,V: Loss of activity."
FT /evidence="ECO:0000269|PubMed:25697423"
FT MUTAGEN 340
FT /note="G->A,S,V: Loss of activity."
FT /evidence="ECO:0000269|PubMed:25697423"
FT STRAND 15..19
FT /evidence="ECO:0007829|PDB:2FB2"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:2FB2"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 52..64
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 69..75
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 108..117
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 132..139
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 145..158
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 161..169
FT /evidence="ECO:0007829|PDB:2FB2"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 177..187
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 213..223
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 238..243
FT /evidence="ECO:0007829|PDB:2FB2"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 249..253
FT /evidence="ECO:0007829|PDB:2FB2"
FT TURN 255..258
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:2FB2"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 288..293
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 298..310
FT /evidence="ECO:0007829|PDB:2FB2"
FT HELIX 316..327
FT /evidence="ECO:0007829|PDB:2FB2"
SQ SEQUENCE 340 AA; 39078 MW; BDCDFE1014E98306 CRC64;
MVEQIKDKLG RPIRDLRLSV TDRCNFRCDY CMPKEVFGDD FVFLPKNELL TFDEMARIAK
VYAELGVKKI RITGGEPLMR RDLDVLIAKL NQIDGIEDIG LTTNGLLLKK HGQKLYDAGL
RRINVSLDAI DDTLFQSINN RNIKATTILE QIDYATSIGL NVKVNVVIQK GINDDQIIPM
LEYFKDKHIE IRFIEFMDVG NDNGWDFSKV VTKDEMLTMI EQHFEIDPVE PKYFGEVAKY
YRHKDNGVQF GLITSVSQSF CSTCTRARLS SDGKFYGCLF ATVDGFNVKA FIRSGVTDEE
LKEQFKALWQ IRDDRYSDER TAQTVANRQR KKINMNYIGG
