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Literature summary for 1.16.1.8 extracted from

  • Wolthers, K.R.; Lou, X.; Toogood, H.S.; Leys, D.; Scrutton, N.S.
    Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry (2007), Biochemistry, 46, 11833-11844.
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
MSR NADP(H)/FAD domain complex, sitting drop vapor diffusion method, 4°C, 10 mg/ml protein in 10 mM Tris/HCl, pH 8.0, 0.5 mM DTT, 1 mM EDTA, and 0.05% NaN3, reservoir solution comprising 0.1 M Tris/HCl, pH 7.5, 0.2 M KBr, and 15% PEG 4000, crystal soaking in saturated NADP+ solution, X-ray diffraction structure determination and analysis at 1.9 A resolution Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2',5'-ADP inhibition of MSR-catalyzed reduction of cytochrome c3+ Homo sapiens
NADP+ inhibition of MSR-catalyzed reduction of cytochrome c3+ Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information isothermal titration calorimetry reveals a binding constant of 0.037 and 0.002 mM for binding of NADP+ and 2',5'-ADP, respectively, for the ligand-protein complex formed with full-length MSR or the isolated FNR module Homo sapiens
0.00289
-
NADPH pH 7.5, 25°C Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
78000
-
x * 78000, SDS-PAGE Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens biological implications of an attenuated mechanism of MS reactivation by MSR on methionine and folate metabolism, overview ?
-
?
[methionine synthase]-methylcob(I)alamin + S-adenosylhomocysteine + NADP+ Homo sapiens
-
[methionine synthase]-cob(II)alamin + NADPH + S-adenosyl-L-methionine
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information biological implications of an attenuated mechanism of MS reactivation by MSR on methionine and folate metabolism, overview Homo sapiens ?
-
?
additional information the enzyme catalyzes also the inhibition of reduction of cytochrome c3+ Homo sapiens ?
-
?
[methionine synthase]-methylcob(I)alamin + S-adenosylhomocysteine + NADP+
-
Homo sapiens [methionine synthase]-cob(II)alamin + NADPH + S-adenosyl-L-methionine
-
r
[methionine synthase]-methylcob(I)alamin + S-adenosylhomocysteine + NADP+ MSR is a flavoprotein that regenerates the active form of cobalamin-dependent methionine synthase Homo sapiens [methionine synthase]-cob(II)alamin + NADPH + S-adenosyl-L-methionine
-
r

Subunits

Subunits Comment Organism
? x * 78000, SDS-PAGE Homo sapiens
More the NADP+-bound FNR-like module of MSR spans the NADP(H)-binding domain, the FAD-binding domain, the connecting domain, and part of the extended hinge region Homo sapiens

Synonyms

Synonyms Comment Organism
Methionine synthase reductase
-
Homo sapiens
MSR
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.92
-
NADPH pH 7.5, 25°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FAD MSR contains one FAD and one FMN cofactor per polypeptide and functions in the sequential transfer of reducing equivalents from NADPH to MS via its flavin centers Homo sapiens
FMN MSR contains one FAD and one FMN cofactor per polypeptide and functions in the sequential transfer of reducing equivalents from NADPH to MS via its flavin centers Homo sapiens
additional information NAD(H) is a poor cofactor Homo sapiens
NADP+ dependent on, binding structure, overview, the NADP+-bound FNR-like module of MSR spans the NADP(H)-binding domain, the FAD-binding domain, the connecting domain, and part of the extended hinge region Homo sapiens
NADPH dependent on, binding structure, overview, the NADP+-bound FNR-like module of MSR spans the NADP(H)-binding domain, the FAD-binding domain, the connecting domain, and part of the extended hinge region Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information steady-state inhibition studies Homo sapiens
0.0014
-
2',5'-ADP inhibition of reduction of cytochrome c3+ Homo sapiens
0.036
-
NADP+ inhibition of reduction of cytochrome c3+ Homo sapiens