7kiz

From Proteopedia

reduced human peroxiredoxin 2

Structural highlights

7kiz is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PRDX2_HUMAN Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system. It is not able to receive electrons from glutaredoxin. May play an important role in eliminating peroxides generated during metabolism. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2).

Publication Abstract from PubMed

Peroxiredoxin 2 (Prdx2) is a thiol peroxidase with an active site Cys (C52) that reacts rapidly with H2O2 and other peroxides. The sulfenic acid product condenses with the resolving Cys (C172) to form a disulfide which is recycled by thioredoxin or GSH via mixed disulfide intermediates, or undergoes hyperoxidation to the sulfinic acid. C172 lies near the C-terminus, outside the active site. It is not established whether structural changes in this region, such as mixed disulfide formation, affect H2O2 reactivity. To investigate, we designed mutants to cause minimal (C172S) or substantial (C172D and C172W) structural disruption. Stopped flow kinetics and mass spectrometry showed that mutation to Ser had minimal effect on rates of oxidation and hyperoxidation whereas Asp and Trp decreased both by approximately 100-fold. To relate to structural changes, we solved the crystal structures of reduced wild-type and C172S Prdx2. The wild-type structure is highly similar to that of the published hyperoxidized form. C172S is closely related but more flexible and, as demonstrated by size exclusion chromatography and analytical ultracentrifugation, a weaker decamer. SEC and AUC showed that the C172D and C172W mutants are also weaker decamers than wild-type and small-angle X-ray scattering analysis indicated greater flexibility with partially unstructured regions consistent with C-terminal unfolding. We propose that these structural changes around C172 negatively impact the active site geometry to decrease reactivity with H2O2. This is relevant for Prdx turnover as intermediate mixed disulfides with C172 would also be disruptive, and could potentially react with peroxides before resolution is complete.

Modifying the resolving cysteine affects the structure and hydrogen peroxide reactivity of peroxiredoxin 2.,Peskin AV, Meotti FC, Kean KM, Gobl C, Peixoto AS, Pace PE, Horne CR, Heath SG, Crowther JM, Dobson RCJ, Karplus PA, Winterbourn CC J Biol Chem. 2021 Mar 2:100494. doi: 10.1016/j.jbc.2021.100494. PMID:33667550^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Peskin AV, Meotti FC, Kean KM, Gobl C, Peixoto AS, Pace PE, Horne CR, Heath SG, Crowther JM, Dobson RCJ, Karplus PA, Winterbourn CC. Modifying the resolving cysteine affects the structure and hydrogen peroxide reactivity of peroxiredoxin 2. J Biol Chem. 2021 Mar 2:100494. doi: 10.1016/j.jbc.2021.100494. PMID:33667550 doi:http://dx.doi.org/10.1016/j.jbc.2021.100494