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 02-SEP-2026, entry version 120. 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; Bacillati; Bacillota; Bacilli; Caryophanales; 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=GTP + AH2 + S-adenosyl-L-methionine = (8S)-3',8-cyclo-7,8- CC dihydroguanosine 5'-triphosphate + 5'-deoxyadenosine + L-methionine + CC A + H(+); Xref=Rhea:RHEA:49576, ChEBI:CHEBI:13193, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17319, ChEBI:CHEBI:17499, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:57844, ChEBI:CHEBI:59789, ChEBI:CHEBI:131766; CC EC=4.1.99.22; Evidence={ECO:0000269|PubMed:23627491, CC 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}. 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; CP000253; ABD31551.1; -; Genomic_DNA. DR RefSeq; WP_000230173.1; NC_007795.1. 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 PDB; 9EFO; NMR; -; A=330-340. DR AlphaFoldDB; P69848; -. DR SMR; P69848; -. DR STRING; 93061.SAOUHSC_02536; -. DR PaxDb; 93061-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 OrthoDB; 9763993at2; -. DR BRENDA; 4.1.99.22; 3352. DR UniPathway; UPA00344; -. DR EvolutionaryTrace; P69848; -. DR PRO; PR:P69848; -. DR Proteomes; UP000008816; Chromosome. 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:InterPro. DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IEA:UniProtKB-UniRule. DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd01335; Radical_SAM; 1. DR CDD; cd21117; Twitch_MoaA; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR HAMAP; MF_01225_B; MoaA_B; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR006638; Elp3/MiaA/NifB-like_rSAM. DR InterPro; IPR013483; MoaA. DR InterPro; IPR040064; MoaA-like. DR InterPro; IPR000385; MoaA_NifB_PqqE_Fe-S-bd_CS. DR InterPro; IPR010505; MoaA_twitch. DR InterPro; IPR050105; MoCo_biosynth_MoaA/MoaC. DR InterPro; IPR007197; rSAM. DR InterPro; IPR058240; rSAM_sf. DR NCBIfam; TIGR02666; moaA; 1. DR PANTHER; PTHR22960:SF0; MOLYBDENUM COFACTOR BIOSYNTHESIS PROTEIN 1; 1. DR PANTHER; PTHR22960; MOLYBDOPTERIN COFACTOR SYNTHESIS PROTEIN A; 1. DR Pfam; PF06463; Mob_synth_C; 1. DR Pfam; PF04055; Radical_SAM; 1. DR SFLD; SFLDF00276; cyclic_pyranopterin_phosphate; 1. DR SFLD; SFLDG01383; cyclic_pyranopterin_phosphate; 1. DR SFLD; SFLDG01386; main_SPASM_domain-containing; 1. DR SFLD; SFLDS00029; Radical_SAM; 1. DR SFLD; SFLDG01067; SPASM/twitch_domain_containing; 1. DR SMART; SM00729; Elp3; 1. DR SUPFAM; SSF102114; Radical SAM enzymes; 1. DR PROSITE; PS01305; MOAA_NIFB_PQQE; 1. DR PROSITE; PS51918; RADICAL_SAM; 1. DR PDBsum; 1TV7; -. DR PDBsum; 1TV8; -. DR PDBsum; 2FB2; -. DR PDBsum; 2FB3; -. DR PDBsum; 9EFO; -. 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 43..45 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..173 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 HELIX 229..231 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 284..286 FT /evidence="ECO:0007829|PDB:1TV7" 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 //