Mechanistic complexities of sulfite oxidase: An enzyme with multiple domains, subunits, and cofactors.

Autor: Enemark JH; Department of Chemistry and Biochemistry, The University of Arizona, 1306 East University Blvd, Tucson, AZ 85721-0041, United States of America. Electronic address: jenemark@arizona.edu.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2023 Oct; Vol. 247, pp. 112312. Date of Electronic Publication: 2023 Jul 04.
DOI: 10.1016/j.jinorgbio.2023.112312
Abstrakt: Sulfite oxidase (SO) deficiency, an inherited disease that causes severe neonatal neurological problems and early death, arises from defects in the biosynthesis of the molybdenum cofactor (Moco) (general sulfite oxidase deficiency) or from inborn errors in the SUOX gene for SO (isolated sulfite oxidase deficiency, ISOD). The X-ray structure of the highly homologous homonuclear dimeric chicken sulfite oxidase (cSO) provides a template for locating ISOD mutation sites in human sulfite oxidase (hSO). Catalysis occurs within an individual subunit of hSO, but mutations that disrupt the hSO dimer are pathological. The catalytic cycle of SO involves five metal oxidation states (Mo VI , Mo V , Mo IV , Fe III , Fe II ), two intramolecular electron transfer (IET) steps, and couples a two-electron oxygen atom transfer reaction at the Mo center with two one-electron transfers from the integral b-type heme to exogenous cytochrome c, the physiological oxidant. Several ISOD examples are analyzed using steady-state, stopped-flow, and laser flash photolysis kinetics and physical measurements of recombinant variants of hSO and native cSO. In the structure of cSO, Mo … Fe = 32 Å, much too long for efficient IET through the protein. Interdomain motion that brings the Mo and heme centers closer together to facilitate IET is supported indirectly by decreasing the length of the interdomain tether, by changes in the charges of surface residues of the Mo and heme domains, as well as by preliminary molecular dynamics calculations. However, direct dynamic measurements of interdomain motion are in their infancy.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. John H. Enemark reports a relationship with The University of Arizona that includes: non-financial support. I was on the Editorial Board of the Journal of Inorganic Biochemistry about 10 years ago. None paying.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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