1gd3
refined solution structure of human cystatin A
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OverviewOverview
The effect of substituting Pro25, located in the alpha-helical region of, the cystatin A structure, with Ser has been studied. The structures of, wild type and P25S cystatin A were determined by multidimensional NMR, spectroscopy under comparable conditions. These two structures were, virtually identical, and the alpha-helix between Glu15-Lys30 exists with, uninterrupted continuity, with a slight bend at residue 25. In order to, characterize the possible substitution effects of Pro25 with Ser on the, alpha-helix, the chemical shifts of the amide nitrogens and protons, the, generalized order parameters obtained by the analyses of the 15N-1H, relaxation data, the amide proton exchange rates, and the NOE networks, among the alpha-helical and surrounding residues were carefully compared., None of these parameters indicated any significant static or dynamic, structural differences between the alpha-helical regions of the wild-type, and P25S cystatin A proteins. We therefore conclude that our previous, structure of the wild-type cystatin A, in which the alpha-helix exhibited, a sharp kink at Pro25, must be revised. The asymmetric distribution of, hydrophobic interactions between the side-chain residues of the, alpha-helix and the rolled beta-sheet surface, as revealed by NOEs, may be, responsible for the slight bend of the alpha-helix in both variants and, for the destabilized hydrogen bonding of the alpha-helical residues that, follow Pro25/Ser25, as evidenced by increased amide exchange rates.
About this StructureAbout this Structure
1GD3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural comparison between wild-type and P25S human cystatin A by NMR spectroscopy. Does this mutation affect the alpha-helix conformation?, Shimba N, Kariya E, Tate S, Kaji H, Kainosho M, J Struct Funct Genomics. 2000;1(1):26-42. PMID:12836678
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