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Victoria A Higman

Publications and source records attributed to Victoria A Higman.

5 recordsLinked to original sources
PubMed2006

His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form.

A polymorphism in complement factor H has recently been associated with age-related macular degeneration (AMD), the leading cause of blindness in the elderly. A histidine rather than a tyrosine at residue position 384 in the mature protein increases the risk of AMD. Here, using a recombinant construct, we show that amino acid 384 is adjacent to a heparin-binding site in CCP7 of factor H and demonstrate that the allotypic variants differentially recognize heparin. This functional alteration may affect binding of factor H to polyanionic patterns on host surfaces, potentially influencing complement activation, immune complex clearance, and inflammation in the macula of AMD patients.

Alleles↗
PubMed2004

Asparagine and glutamine side-chain conformation in solution and crystal: a comparison for hen egg-white lysozyme using residual dipolar couplings.

Experimental (15)N-(1)H and (1)H-(1)H residual dipolar couplings (RDCs) for the asparagine (Asn) and glutamine (Gln) side chains of hen egg-white lysozyme are measured and analysed in conjunction with (1)N relaxation data, information about chi(1) torsion angles in solution and molecular dynamics simulations. The RDCs are compared to values predicted from 16 high-resolution crystal structures. Two distinct groups of Asn and Gln side chains are identified. The first contains residues whose side chains show a fixed, relatively rigid, conformation in solution. For these residues there is good agreement between the experimental and predicted RDCs. This agreement improves when the experimental order parameter, S, is included in the calculation of the RDCs from the crystal structures. The comparison of the experimental RDCs with values calculated from the X-ray structures shows that the similarity between the oxygen and nitrogen electron densities is a limitation to the correct assignment of the Asn and Gln side-chain orientation in X-ray structures. In the majority of X-ray structures a 180 degrees rotation about chi(2) or chi(3), leading to the swapping of N(delta/epsilon 2) and O(delta/epsilon 1), is necessary for at least one Asn or Gln residue in order to achieve good agreement between experimental and predicted RDCs. The second group contains residues whose side chains do not adopt a single, well-defined, conformation in solution. These residues do not show a correlation between the experimental and predicted RDCs. In many cases the family of crystal structures shows a range of orientations for these side chains, but in others the crystal structures show a well-defined side-chain position. In the latter case, this is found to arise from crystallographic contacts and does not represent the behaviour of the side chain in solution.

Animals↗
PubMed2003

Uncovering network systems within protein structures.

Traditionally, proteins have been viewed as a construct based on elements of secondary structure and their arrangement in three-dimensional space. In a departure from this perspective we show that protein structures can be modelled as network systems that exhibit small-world, single-scale, and to some degree, scale-free properties. The phenomenological network concept of degrees of separation is applied to three-dimensional protein structure networks and reveals how amino acid residues can be connected to each other within six degrees of separation. This work also illuminates the unique features of protein networks in comparison to other networks currently studied. Recognising that proteins are networks provides a means of rationalising the robustness in the overall three-dimensional fold of a protein against random mutations and suggests an alternative avenue to investigate the determinants of protein structure, function and folding.

Models, Molecular↗