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COVER: X-ray crystal structure of human serum albumin with C18:0 (left) in the presumed highest affinity binding sites for long-chain fatty acids (labeled 1-5); C18:0 is present in site 3 but not visible. The three domains (I-III) and the two subdomains of each domain (A, B) of albumin are labeled. On the right, C26:0 has modeled into the same sites. The methylene tail (yellow) of C26:0 protrudes extensively into the water in four of the sites, but site 3 is not large enough to accommodate a fatty acid of this length. The modeling experiment suggests that none of the 5 sites are suitable for C26:0; the NMR data show a single binding site for C26:0 on BSA that may well represent a binding configuration that is distinct from those observed crystallographically for long-chain fatty acids up to C20. (See Choi et al., p. 1000.)
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