Biomedical subjects
Publications and source records attributed to C S Liu.
We have shown that an unusual morphological thinning of the anterior clear zone of the lens is found in patients with gout on long term Allopurinol therapy. The significance of this is discussed.
A basic phospholipase A2 (PLA2) was isolated and purified from the venom of Bungarus fasciatus. Four kinds of enzymes, lysyl endopeptidase, endoproteinase Asp-N, endoproteinase Glu-C and trypsin, were employed to elucidate the complete primary structure by means of gas-phase sequencing. The amino-acid sequence reveals 118 amino-acid residues containing seven pairs of half-cystine. It has 78% and 61% structural identities with PLA2 from Bungarus multicinctus and Naja melanoleuca DE-II, respectively.
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Heparin binds to human antithrombin III and accelerates its inhibitory activity in the blood coagulation system. Previous reports (Rosenberg, R. D., and Damus, P. S. (1973) J. Biol. Chem. 248, 6490-6505; Pecon, J. M., and Blackburn, M. N. (1984) J. Biol. Chem. 259, 935-938) have shown that selective chemical modification of a limited number of lysine residues in antithrombin III causes drastic loss of its heparin cofactor activity. We have performed chemical modification of antithrombin III with trinitrobenzene sulfonic acid in order to determine the location of these lysine residues. When antithrombin III was treated with 100 M excess of trinitrobenzene sulfonic acid for 10 min, about 3.2 mol of amino group per mol of antithrombin III were modified. The heparin cofactor activity dropped to about 25%, whereas the progressive inhibitory activity (in the absence of heparin) remained essentially intact (about 95%). The modified amino groups were identified to be Lys114 (75%), Lys125 (94%), and Lys287 (96%). These results were obtained by comparing and analyzing the cyanogen bromide fragments derived from native antithrombin III and the 10-min modified antithrombin III. When antithrombin III was pretreated with heparin, followed by trinitrobenzene sulfonic acid modification, the extent of modification at Lys114 and Lys125 decreased from 75% and 94% to 20% and 40%, respectively, whereas the modification at Lys287 remained nearly quantitative (greater than 95%). Based on these results, we conclude that Lys114 and Lys125 are essential for the heparin cofactor activity of human antithrombin III.
From structural analysis on genetically abnormal and chemically modified human antithrombin III [Koide, T., Odani, S., Takahashi, K., Ono, T. and Sakuragawa, N. (1984) Proc. Natl Acad. Sci. USA 81, 289-293; Chang, J.-Y. and Tran, T. H., (1986) J. Biol. Chem. 261, 1174-1176; Blackburn, M. N., Smith, R. L., Carson, J. and Sibley, C. C. (1984) J. Biol. Chem. 259, 939-941], the heparin-binding site of antithrombin III has been suggested to be in the region of Pro-41, Arg-47 and Trp-49. In this study the heparin-binding site was probed by preferential cleavage of V8 protease on heparin-treated and non-treated native antithrombin III. The study has been based on the presumption that the heparin-binding site of antithrombin III is situated at exposed surface domain and may be preferentially attacked during limited proteolytic digestion. Partially digested antithrombin III samples were monitored by quantitative amino-terminal analysis and amino acid sequencing to identify the preferential cleavage sites. 1-h-digested antithrombin III was separated on HPLC and peptide fragments were isolated and characterized both qualitatively and quantitatively. The results reveal that Glu-Gly (residues 34-35), Glu-Ala (residues 42-43) and Glu-Leu (residues 50-51) are three preferential cleavage sites for V8 protease and their cleavage, especially the Glu-Ala and the Glu-Leu sites, was drastically inhibited when antithrombin III was preincubated with heparin. Both high-affinity and low-affinity antithrombin-III-binding heparins were shown to inhibit the V8 protease digestion of native antithrombin III, but the high-affinity sample exhibited a higher inhibition activity than the low-affinity heparin. These findings (a) imply that the segment containing residues 34-51 is among the most exposed region of native antithrombin III and (b) support the previous conclusions that this region may play a pivotal role in the heparin binding.
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Two analogous protease inhibitors, VIIIb and IX in the venom of Bungarus fasciatus were reduced and carboxymethylated. Tryptic peptides were separated by cellulose thin-layer peptide mapping technique, and amino acid sequences were analyzed by DABITC/PITC double coupling method. Alignment of all tryptic peptides was established by analyses of chymotryptic peptides and further confirmed by Staphylococcus aureus V8 protease digestion. IX consisted of 65 amino acid residues. VIIIb consisted of 62 residues, identical to the N-terminal 62-amino acid sequence of IX.
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A hemoglobin variant with the slightly fast mobility associated with K hemoglobins was found, together with hemoglobin S, in an apparently healthy 3-year-old Negro girl from Washington, D.C. Her father had the same variant, along with hemoglobin A, and her mother had hemoglobins A plus S. Respective proportions of hemoglobins K and S in the propositus were 66-34. The K variant now has been found to have the structural change Gln yields Glu at position beta-131 (beta-H9); therefore it apparently is identical to hemoglobin Camden reported in trait form in a Negro subject by YATES, BELLINGHAM and HUEHNS (Nature 243: 467-468, 1973).
One of the 2 main hemoglobins of the sea snake Pelamis platurus, (the Yellow-bellied sea snake) comprising about 70% of the total hemoglobin, was separated by DEAE-Sephadex column chromatography. From results of gel filtration and iron content determination, both intact sea snake hemoglobin, and the isolated major hemoglobin, were concluded to be composed of 4 subunits with a molecular weight of 66,000-67,000 daltons. Separation of the chains of globin of the major hemoglobin by CM 52 column chromatography gave 3 peaks, named, chains a, b, and c. The approximate molecular weights of chains a, b, and c were deduced by SDS gel electrophoresis to be 14,000, 16,000, and 20,000 daltons, respectively. The peptide maps and amino acid compositions of the three chains were distinctly different. N-Terminal and C-terminal amino acid sequence studies reveal that chains a, b, and c represented the alpha-chain, beta-chain, and beta'-chain differing from the normal beta-chain in having a C-terminal sequence of -Arg-Leu-His-Tyr. From the peak areas of the 3 chains obtained by CM 52 column chromatography, and the peak sizes of the 3 bands separated by SDS gel electrophoresis, it was concluded that the sea snake hemoglobin is composed of a hybrid tetramer, alpha2betabeta'.
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