James E. Pitts
Laboratory of Molecular Biology
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Featured researches published by James E. Pitts.
Scandinavian Journal of Clinical & Laboratory Investigation | 1992
James E. Pitts; V. Dhanaraj; C.G. Dealwis; Dimitris Mantafounis; Philip Nugent; P. Orprayoon; J. B. Cooper; M. P. Newman; Tom L. Blundell
The specificity and pH profile of aspartic proteinases have evolved to include not only pepsin with a broad specificity and an optimal activity in acid media, but also renin, with high specificity for angiotensinogen and activity close to neutral pH. Comparisons of the structures and catalytic activities of aspartic proteinases provide helpful clues for engineering new activity profiles. We illustrate an approach that involves recombinant DNA techniques, biochemistry, structure determination and biocomputing. We use the 3-D structures of inhibitor complexes of several aspartic proteinases to define likely intermediates and specificity sub-sites. The multidisciplinary research is organised as cycles, in which each cycle tests a design hypothesis proposed in the previous cycle. We use one member of the aspartic proteinase family, chymosin, to illustrate these ideas in engineering enzymes with altered pH optima and specificities.
FEBS Letters | 1980
James E. Pitts; S.P. Wood; L. Hearn; I.J. Tickle; C.W. Wu; Tom L. Blundell; I.C.A.F. Robinson
The hormones oxytocin and vasopressin are stored in the neurosecretory granules of the neurohypophysis bound to acidic 10 000 mol. wt proteins called neurophysins. Three major neurophysins can be extracted from the porcine pituitary. The amino acid sequences of forms I and III are very similar, form I being a truncated form of III with three residues removed from the C-terminus [I 3. The physiological role of neurophysins is poorly understood. They are secreted with the hormones into the bled-strew where they circulate in an uncomplexed form. ~tra~llularly, they may stabilise the hormones during intra-axonal transport and storage by preventing leakage, enzymatic degradation and reduction of the susceptible 1-6 disulphide bond. The protein also concentrates the hormones in an insoluble form until required and reduces osmotic problems in the storage compartment . Neurophysins represent a family of proteins that show a highly conserved central core sequence with marked variability at the aminoand c~boxyl-terra both within and between species. The chemical specificity for ligand binding has been porously studied and there is a large amount of kin&G information derived from spectroscopic and thermodynamic studies [2]. The structure analysis of neurophysin bound to a hormone peptide analogue should contribute to the understanding of many biochemical questions. This structure might provide a rare opportunity to define
Proceedings of the National Academy of Sciences of the United States of America | 1981
Tom L. Blundell; James E. Pitts; I.J. Tickle; S.P. Wood; C.W. Wu
FEBS Journal | 1984
Ian D. Glover; David J. Barlow; James E. Pitts; S.P. Wood; I.J. Tickle; Tom L. Blundell; Kazuhiko Tatemoto; Joe R. Kimmel; Axel Wollmer; Wolfgang Strassburger; You‐Shang Zhang
FEBS Journal | 1983
M Bajaj; Tom L. Blundell; James E. Pitts; S.P. Wood; Tatnell Ma; Falkmer S; Emdin So; Linda K. Gowan; Crow H; Christian Schwabe
FEBS Journal | 1977
S.P. Wood; James E. Pitts; Tom L. Blundell; I.J. Tickle; John A. Jenkins
Biochemical Journal | 1986
M Bajaj; Tom L. Blundell; R. Horuk; James E. Pitts; S.P. Wood; Linda K. Gowan; Christian Schwabe; Axel Wollmer; J. Gliemann; S. Gammeltoft
Philosophical Transactions of the Royal Society B | 1989
Tom L. Blundell; G. Elliott; S. P. Gardner; Tim Hubbard; Suhail A. Islam; Mark Johnson; Dimitris Mantafounis; Peter Murray-Rust; John P. Overington; James E. Pitts; Andrej Šali; B. L. Sibanda; Juswinder Singh; Michael J. E. Sternberg; Michael J. Sutcliffe; Janet M. Thornton; P. Travers
Critical Reviews in Biochemistry and Molecular Biology | 1982
Tom L. Blundell; James E. Pitts; S.P. Wood
Advances in Experimental Medicine and Biology | 1998
Armando Albert; Tom L. Blundell; Dhanaraj; Luis Enrique Donate; Matthew Groves; Kunchur Guruprasad; Philip Nugent; Poonsook Orprayoon; James E. Pitts; Stephen D. Rufino; Narayanaswamy Srinivasan; Mark G. Williams; Wilsher J