UniProt functional annotation for Q1LRY0



	UniProt functional annotation for Q1LRY0

UniProt code: Q1LRY0.

Organism: Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / CH34) (Ralstonia metallidurans).

Taxonomy: Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales; Burkholderiaceae; Cupriavidus.

Function: Catalyzes the reversible interconversion of isobutyryl-CoA and n-butyryl-CoA, and to a much lesser extent, of pivalyl-CoA and isovaleryl-CoA, using radical chemistry (PubMed:22167181). Also exhibits GTPase activity, associated with its G-protein domain (MeaI) that functions as a chaperone that assists cofactor delivery and proper holo-enzyme assembly (PubMed:22167181, PubMed:25675500). The G-domain of IcmF has also a role in its cofactor repair (PubMed:28130442). Does not display ATPase activity. {ECO:0000269|PubMed:22167181, ECO:0000269|PubMed:25675500, ECO:0000269|PubMed:28130442}.

Catalytic activity: Reaction=2-methylpropanoyl-CoA = butanoyl-CoA; Xref=Rhea:RHEA:13141, ChEBI:CHEBI:57338, ChEBI:CHEBI:57371; EC=5.4.99.13; Evidence={ECO:0000255|HAMAP-Rule:MF_02050, ECO:0000269|PubMed:22167181};

Catalytic activity: Reaction=3-methylbutanoyl-CoA = 2,2-dimethylpropanoyl-CoA; Xref=Rhea:RHEA:52620, ChEBI:CHEBI:57345, ChEBI:CHEBI:136712; Evidence={ECO:0000269|PubMed:22167181};

Catalytic activity: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000255|HAMAP- Rule:MF_02050, ECO:0000269|PubMed:22167181};

Cofactor: Name=adenosylcob(III)alamin; Xref=ChEBI:CHEBI:18408; Evidence={ECO:0000255|HAMAP-Rule:MF_02050, ECO:0000269|PubMed:25675500};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_02050, ECO:0000269|PubMed:25675500};

Activity regulation: Is prone to inactivation during catalytic turnover due to the occasional loss of the 5'-deoxyadenosine moiety and formation of the inactive cob(II)alamin cofactor in its active site. The GTPase activity of IcmF powers the ejection of the inactive cofactor and requires the presence of an acceptor protein, adenosyltransferase (ATR), for receiving it. ATR, in turn, catalyzes an adenosylation reaction converting cob(II)alamin in the presence of ATP and a reductant to the active AdoCbl cofactor. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step, regenerating active enzyme. The GTPase activity of IcmF is significantly decreased in the presence of excess of AdoCbl or cob(II)alamin and is higher in the apoenzyme state, indicating that the G-domain senses the presence and identity of the cofactor in the mutase active site. {ECO:0000269|PubMed:28130442}.

Biophysicochemical properties: Kinetic parameters: KM=40 uM for GTP (at 37 degrees Celsius) {ECO:0000269|PubMed:22167181}; Vmax=0.015 umol/min/mg enzyme for isovaleryl-CoA isomerization (at 37 degrees Celsius) {ECO:0000269|PubMed:22167181}; Vmax=13.8 umol/min/mg enzyme for isobutyryl-CoA isomerization (at 37 degrees Celsius) {ECO:0000269|PubMed:22167181}; Vmax=33.0 umol/min/mg enzyme for n-butyryl-CoA isomerization (at 37 degrees Celsius) {ECO:0000269|PubMed:22167181}; Note=kcat is 18 min(-1) for GTPase activity (at 37 degrees Celsius). {ECO:0000269|PubMed:22167181};

Subunit: Homodimer. {ECO:0000255|HAMAP-Rule:MF_02050, ECO:0000269|PubMed:25675500}.

Domain: Is composed of four functional domains: the N-terminal 5'- deoxyadenosylcobalamin binding region that is homologous to the small subunit of ICM (IcmB), a middle P-loop GTPase domain (MeaI) that acts as a chaperone for ICM, a structured linker region involved in dimer formation, and a C-terminal part that is homologous to the large substrate-binding subunit of ICM (IcmA). {ECO:0000269|PubMed:25675500}.

Miscellaneous: In many AdoCbl-dependent isomerases, e.g. methylmalonyl- CoA mutase (MCM), its G-protein chaperone is a separate protein. {ECO:0000305}.

Similarity: Belongs to the IcmF family. {ECO:0000255|HAMAP- Rule:MF_02050, ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / CH34) (Ralstonia metallidurans).
Taxonomy:		Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales; Burkholderiaceae; Cupriavidus.



Function:		Catalyzes the reversible interconversion of isobutyryl-CoA and n-butyryl-CoA, and to a much lesser extent, of pivalyl-CoA and isovaleryl-CoA, using radical chemistry (PubMed:22167181). Also exhibits GTPase activity, associated with its G-protein domain (MeaI) that functions as a chaperone that assists cofactor delivery and proper holo-enzyme assembly (PubMed:22167181, PubMed:25675500). The G-domain of IcmF has also a role in its cofactor repair (PubMed:28130442). Does not display ATPase activity. {ECO:0000269\|PubMed:22167181, ECO:0000269\|PubMed:25675500, ECO:0000269\|PubMed:28130442}.


Catalytic activity:		Reaction=2-methylpropanoyl-CoA = butanoyl-CoA; Xref=Rhea:RHEA:13141, ChEBI:CHEBI:57338, ChEBI:CHEBI:57371; EC=5.4.99.13; Evidence={ECO:0000255\|HAMAP-Rule:MF_02050, ECO:0000269\|PubMed:22167181};
Catalytic activity:		Reaction=3-methylbutanoyl-CoA = 2,2-dimethylpropanoyl-CoA; Xref=Rhea:RHEA:52620, ChEBI:CHEBI:57345, ChEBI:CHEBI:136712; Evidence={ECO:0000269\|PubMed:22167181};
Catalytic activity:		Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000255\|HAMAP- Rule:MF_02050, ECO:0000269\|PubMed:22167181};
Cofactor:		Name=adenosylcob(III)alamin; Xref=ChEBI:CHEBI:18408; Evidence={ECO:0000255\|HAMAP-Rule:MF_02050, ECO:0000269\|PubMed:25675500};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255\|HAMAP-Rule:MF_02050, ECO:0000269\|PubMed:25675500};
Activity regulation:		Is prone to inactivation during catalytic turnover due to the occasional loss of the 5'-deoxyadenosine moiety and formation of the inactive cob(II)alamin cofactor in its active site. The GTPase activity of IcmF powers the ejection of the inactive cofactor and requires the presence of an acceptor protein, adenosyltransferase (ATR), for receiving it. ATR, in turn, catalyzes an adenosylation reaction converting cob(II)alamin in the presence of ATP and a reductant to the active AdoCbl cofactor. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step, regenerating active enzyme. The GTPase activity of IcmF is significantly decreased in the presence of excess of AdoCbl or cob(II)alamin and is higher in the apoenzyme state, indicating that the G-domain senses the presence and identity of the cofactor in the mutase active site. {ECO:0000269\|PubMed:28130442}.
Biophysicochemical properties:		Kinetic parameters: KM=40 uM for GTP (at 37 degrees Celsius) {ECO:0000269\|PubMed:22167181}; Vmax=0.015 umol/min/mg enzyme for isovaleryl-CoA isomerization (at 37 degrees Celsius) {ECO:0000269\|PubMed:22167181}; Vmax=13.8 umol/min/mg enzyme for isobutyryl-CoA isomerization (at 37 degrees Celsius) {ECO:0000269\|PubMed:22167181}; Vmax=33.0 umol/min/mg enzyme for n-butyryl-CoA isomerization (at 37 degrees Celsius) {ECO:0000269\|PubMed:22167181}; Note=kcat is 18 min(-1) for GTPase activity (at 37 degrees Celsius). {ECO:0000269\|PubMed:22167181};
Subunit:		Homodimer. {ECO:0000255\|HAMAP-Rule:MF_02050, ECO:0000269\|PubMed:25675500}.
Domain:		Is composed of four functional domains: the N-terminal 5'- deoxyadenosylcobalamin binding region that is homologous to the small subunit of ICM (IcmB), a middle P-loop GTPase domain (MeaI) that acts as a chaperone for ICM, a structured linker region involved in dimer formation, and a C-terminal part that is homologous to the large substrate-binding subunit of ICM (IcmA). {ECO:0000269\|PubMed:25675500}.
Miscellaneous:		In many AdoCbl-dependent isomerases, e.g. methylmalonyl- CoA mutase (MCM), its G-protein chaperone is a separate protein. {ECO:0000305}.
Similarity:		Belongs to the IcmF family. {ECO:0000255\|HAMAP- Rule:MF_02050, ECO:0000305}.