Literature summary for 1.8.98.2 extracted from

Forshaw, T.E.; Reisz, J.A.; Nelson, K.J.; Gumpena, R.; Lawson, J.R.; Joensson, T.J.; Wu, H.; Clodfelter, J.E.; Johnson, L.C.; Furdui, C.M.; Lowther, W.T.
Specificity of human sulfiredoxin for reductant and peroxiredoxin oligomeric state (2021), Antioxidants (Basel), 10, 946 .

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified Srx-Prx1 complex, hanging drop vapor diffusion method, mixing of 10 mg/ml protein in 20 mM HEPES, pH 7.5, 100 mM NaCl with well solution containing 100 mM citric acid, pH 4.5, 26% PEG 400, and 100 mM CsCl, X-ray diffraction structure determination and analysis at 3.0 A resolution, molecular replacement and modeling by superimposing five dimeric Srx-Prx1 complexes (PDB entry 2RII) onto the five Prx dimers within the decameric Prx2-SO2H (PDB ID 1QMV) structure. The entire active site helix of Prx1 (residues 46-69) and the C-terminus (residues 169-199) are removed from the search model to reduce bias. Two decamers, each containing ten Prx and ten Srx molecules (five Prx dimers and ten Srx monomers), are found in the asymmetric unit, consistent with the observed self-rotation function. Additional crystallization of hyperoxidized Prx2 and Prx3 variants	Homo sapiens

Crystallization (Comment)

Organism

purified Srx-Prx1 complex, hanging drop vapor diffusion method, mixing of 10 mg/ml protein in 20 mM HEPES, pH 7.5, 100 mM NaCl with well solution containing 100 mM citric acid, pH 4.5, 26% PEG 400, and 100 mM CsCl, X-ray diffraction structure determination and analysis at 3.0 A resolution, molecular replacement and modeling by superimposing five dimeric Srx-Prx1 complexes (PDB entry 2RII) onto the five Prx dimers within the decameric Prx2-SO2H (PDB ID 1QMV) structure. The entire active site helix of Prx1 (residues 46-69) and the C-terminus (residues 169-199) are removed from the search model to reduce bias. Two decamers, each containing ten Prx and ten Srx molecules (five Prx dimers and ten Srx monomers), are found in the asymmetric unit, consistent with the observed self-rotation function. Additional crystallization of hyperoxidized Prx2 and Prx3 variants

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	Srx mutant variants analyzed by circular dichroism spectroscopy (JASCO-720) in 20 mM HEPES, pH 7.5, 100 mM NaCl at a concentration from 0.4 mg/ml are confirmed to exhibit wild-type-like spectra	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH	Homo sapiens	-	peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9BYN0	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	specificity of human sulfiredoxin for reductant and peroxiredoxin oligomeric state, overview. The resolution of the Prx-Srx complex involves the reduction of the thiosulfinate intermediate (Prx-CP-S=O-S-Srx) to yield the Prx Cys-sulfenic acid intermediate (Prx-CP-SOH). Yeast Srx contains an adjacent resolving Cys residue (Cys-SR) that can react with the thiosulfinate intermediate leading to the formation of an Srx intramolecular disulfide (Srx-(S-S)). In contrast, human Srx has only one Cys residue and requires an exogenous reductant. Possible reductants include the Trx system (Trx/TrxR/NADPH), glutathione (GSH) and hydrogen sulfide (H2S), these reductants would ultimately yield reduced Srx (Srx-SH). Enzyme-substrate binding studies with mutant Prx1 (e.g. Prx1 C83V and Prx1 C71S/C173S). Repair of hyperoxidized Prx2, Prx3 and their chimeras, the C-terminal sequence differences between Prx2 and Prx3 impact the rate of repair by Srx	Homo sapiens	?	-	-
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 DTT	-	Homo sapiens	peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + DTT disulfide	-	?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 GSH	combined GSH and H2S for the repair of cytosolic Prx2	Homo sapiens	peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + G-S-S-G	-	?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 H2S	preference for H2S to support the repair of mitochondrial hyperoxidized Prx3 by Srx. Combined GSH and H2S for the repair of cytosolic Prx2	Homo sapiens	peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + HS-SH	-	?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH	-	Homo sapiens	peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R	-	?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH	hyperoxidized Prx1	Homo sapiens	peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R	-	?

Subunits

Subunits	Comment	Organism
More	the decameric Srx-Prx1 complex reveals extended binding interface, human Prx1 and Prx2 form a decameric toroid	Homo sapiens

Synonyms

Synonyms	Comment	Organism
Srx	-	Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

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

General Information

General Information	Comment	Organism
malfunction	loss of the extended active site interface within engineered peroxiredoxin isozymes, Prx2 and Prx3, dimers yields variants more resistant to hyperoxidation and repair by enzyme Srx	Homo sapiens
additional information	the decameric Srx-Prx1 complex reveals extended binding interface, human Prx1 and Prx2 form a decameric toroid. The crystal structure of the toroidal Prx1-Srx complex shows an extended active site interface. Structural basis for the ability of Srx to reduce the hyperoxidized form of human Prxs, juxtaposition of the two active-site interfaces of the two proteins and wrapping of the Prx C-terminus around Srx in an essential interaction, overview	Homo sapiens
physiological function	the repair and reactivation of the hyperoxidized Prxs by Srx is an important cellular process, hydrogen sulfide repair of hyperoxidized 2-Cys Prxs by human sulfiredoxin (Srx), structural requirements, peroxiredoxin catalytic and sulfiredoxin repair cycles, detailed overview. The physiological reductants hydrogen sulfide (H2S) and glutathione (GSH) show relative efficacy in this reaction. Prx isoform-dependent use of and potential cooperation between GSH and H2S in supporting Srx activity	Homo sapiens