6DUJ

Crystal structure of A51V variant of Human Cytochrome c

Summary for 6DUJ

• Entry DOI: 10.2210/pdb6duj/pdb
• Descriptor: Cytochrome c, HEME C (3 entities in total)
• Functional Keywords: peroxidase activity, heme, apoptosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 24574.28

Authors

Lei, H.,Bowler, B.E. (deposition date: 2018-06-20, release date: 2019-06-26, Last modification date: 2024-10-23)

Primary citation

Lei, H.,Bowler, B.E.
Naturally Occurring A51V Variant of Human CytochromecDestabilizes the Native State and Enhances Peroxidase Activity.
J.Phys.Chem.B, 123:8939-8953, 2019

PubMed Abstract: The A51V variant of human cytochrome is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of the A51V variant shows only minor changes in tertiary structure relative to the wild-type (WT) protein. Guanidine hydrochloride denaturation demonstrates that the global stability of the A51V variant is 1.3 kcal/mol less than that of the WT protein. The midpoint pH, pH, of the alkaline transition of the A51V variant is 1 unit less than that of the WT protein. Stopped-flow pH jump experiments show that the A51V substitution affects the triggering ionization for one of two kinetically distinguishable alkaline conformers and enhances the accessibility of a high-spin heme transient. The pH for acid unfolding of the A51V variant is 0.7 units higher than for that of the WT protein. Consistent with the greater accessibility of non-native conformers for the A51V variant, the values for its peroxidase activity increase by 6- to 15-fold in the pH range of 5-8 versus those of the WT protein. These data along with previously reported data for the other THC4-linked variants, G41S and Y48H, underscore the role of Ω-loop C (residues 40-57) in modulating the peroxidase activity of cytochrome early in apoptosis.

PubMed: 31557440
DOI: 10.1021/acs.jpcb.9b05869

Experimental method

X-RAY DIFFRACTION (1.82202726164 Å)