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J M Burridge

Publications and source records attributed to J M Burridge.

7 recordsLinked to original sources
PubMed1986

Three-dimensional graphics display of X-ray angiography data.

A method for making three-dimensional computer graphics displays of in vivo blood vessels is described. Input data are taken from biplane X-ray angiograms using an image-processing system. A display list is built up which is then sent to a high-function graphics system. Real-time interaction is possible using a vector-refresh display where the blood vessel segments are shown as cylinders of the appropriate diameter. Realistic raster representations may be used to give the user insight into the overall topology of the network of vessels. The Winchester Graphics System is described together with explanations of the techniques employed.

Angiography↗
PubMed1985

Refined crystal structures of Escherichia coli and chicken liver dihydrofolate reductase containing bound trimethoprim.

Refined crystal structures are reported for complexes of Escherichia coli and chicken dihydrofolate reductase containing the antibiotic trimethoprim (TMP). Structural comparison of these two complexes reveals major geometrical differences in TMP binding that may be important in understanding the stereo-chemical basis of this inhibitor's selectivity for bacterial dihydrofolate reductases. For TMP bound to chicken dihydrofolate reductase we observe an altered binding geometry in which the 2,4-diaminopyrimidine occupies a position in closer proximity (by approximately 1 A) to helix alpha B compared to the pyrimidine position for TMP or methotrexate bound to E. coli dihydrofolate reductase. One important consequence of this deeper insertion of the pyrimidine into the active site of chicken dihydrofolate reductase is the loss of a potential hydrogen bond that would otherwise form between the carbonyl oxygen of Val-115 and the inhibitor's 4-amino group. In addition, for TMP bound to E. coli dihydrofolate reductase, the inhibitor's benzyl side chain is positioned low in the active-site pocket pointing down toward the nicotinamide-binding site, whereas, in chicken dihydrofolate reductase, the benzyl group is accommodated in a side channel running upward and away from the cofactor. As a result, the torsion angles about the C5-C7 and C7-C1' bonds for TMP bound to the bacterial reductase (177 degrees, 76 degrees) differ significantly from the corresponding angles for TMP bound to chicken dihydrofolate reductase (-85 degrees, 102 degrees). Finally, when TMP binds to the chicken holoenzyme, the Tyr-31 side chain undergoes a large conformational change (average movement is 5.4 A for all atoms beyond C beta), rotating down into a new position where it hydrogen bonds via an intervening water molecule to the backbone carbonyl oxygen of Trp-24.

Animals↗
PubMed1985

Dihydrofolate reductase. The stereochemistry of inhibitor selectivity.

X-ray structural results are reported for 10 triazine and pyrimidine inhibitors of dihydrofolate reductase, each one studied as a ternary complex with NADPH and chicken dihydrofolate reductase. Analysis of these data and comparison with structural results from the preceding paper (Matthews, D.A., Bolin, J.T., Burridge, J.M., Filman, D.J., Volz, K.W., Kaufman, B. T., Beddell, C.R., Champness, J.N., Stammers, D.K., and Kraut, J. (1985) J. Biol. Chem. 260, 381-391) in which we contrasted binding of the antibiotic trimethoprim (TMP) to chicken dihydrofolate reductase on the one hand with its binding to Escherichia coli dihydrofolate reductase on the other, permit identification of differences that are important in accounting for TMP's selectivity. The crystallographic evidence strongly suggests that loss of a potential hydrogen bond between the 4-amino group of TMP and the backbone carbonyl of Val-115 when TMP binds to chicken dihydrofolate reductase but not when it binds to the E. coli reductase is the major factor responsible for this drug's more potent inhibition of bacterial dihydrofolate reductase. A key finding of the current study which is important in understanding why TMP binds differently to chicken and E. coli dihydrofolate reductases is that residues on opposite sides of the active-site cleft in chicken dihydrofolate reductase are about 1.5-2.0 A further apart than are structurally equivalent residues in the E. coli enzyme.

Animals↗
PubMed1982

Computer graphics in drug design: molecular modeling of thyroid hormone-prealbumin interactions.

Computer graphics modeling of the thyroxine-prealbumin complex provides a detailed picture of the interactions between thyroxine and prealbumin. A wide variety of thyroid hormone analogue-prealbumin complexes were modeled by calculating the molecular surfaces of the analogues and the prealbumin hormone-binding site. Analogues with high binding affinity were observed to fill more of the hormone-binding site than low-affinity analogues. These surface models described many aspects of the hormone-protein interaction which were not obvious using simple wire models and led us to develop a model which accounts for thyroid hormone-prealbumin structure-activity relationships and ultimately to predict and measure the relative binding affinities of four previously untested thyroid hormone analogues to prealbumin.

Chemical Phenomena↗