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Primary and Secondary Coordination Sphere Effects on the Structure and Function of S-Nitrosylating Azurin.
Van Stappen, Casey; Dai, Huiguang; Jose, Anex; Tian, Shiliang; Solomon, Edward I; Lu, Yi.
Affiliation
  • Van Stappen C; Department of Chemistry, University of Texas at Austin, 105 E 24th St., Austin, Texas 78712, United States.
  • Dai H; Department of Chemistry, University of Texas at Austin, 105 E 24th St., Austin, Texas 78712, United States.
  • Jose A; Department of Chemistry, University of Urbana-Champaign, Champaign, Illinois 61801, United States.
  • Tian S; Department of Chemistry, Stanford University, Stanford, California 94305-5080, United States.
  • Solomon EI; Department of Chemistry, University of Urbana-Champaign, Champaign, Illinois 61801, United States.
  • Lu Y; Department of Chemistry, Stanford University, Stanford, California 94305-5080, United States.
J Am Chem Soc ; 145(37): 20610-20623, 2023 09 20.
Article in En | MEDLINE | ID: mdl-37696009
Much progress has been made in understanding the roles of the secondary coordination sphere (SCS) in tuning redox potentials of metalloproteins. In contrast, the impact of SCS on reactivity is much less understood. A primary example is how copper proteins can promote S-nitrosylation (SNO), which is one of the most important dynamic post-translational modifications, and is crucial in regulating nitric oxide storage and transportation. Specifically, the factors that instill CuII with S-nitrosylating capabilities and modulate activity are not well understood. To address this issue, we investigated the influence of the primary and secondary coordination sphere on CuII-catalyzed S-nitrosylation by developing a series of azurin variants with varying catalytic capabilities. We have employed a multidimensional approach involving electronic absorption, S and Cu K-edge XAS, EPR, and resonance Raman spectroscopies together with QM/MM computational analysis to examine the relationships between structure and molecular mechanism in this reaction. Our findings have revealed that kinetic competency is correlated with three balancing factors, namely Cu-S bond strength, Cu spin localization, and relative S(ps) vs S(pp) contributions to the ground state. Together, these results support a reaction pathway that proceeds through the attack of the Cu-S bond rather than electrophilic addition to CuII or radical attack of SCys. The insights gained from this work provide not only a deeper understanding of SNO in biology but also a basis for designing artificial and tunable SNO enzymes to regulate NO and prevent diseases due to SNO dysregulation.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Azurin / Metalloproteins Language: En Journal: J Am Chem Soc Year: 2023 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Azurin / Metalloproteins Language: En Journal: J Am Chem Soc Year: 2023 Document type: Article Affiliation country: United States Country of publication: United States