ISSN:
1399-0047
Source:
Crystallography Journals Online : IUCR Backfile Archive 1948-2001
Topics:
Chemistry and Pharmacology
,
Geosciences
,
Physics
Notes:
Myristoyl-CoA–protein N-myristoyltransferase (Nmt; E.C. 2.1.3.97) catalyzes the covalent attachment of myristate to the N-terminal glycine amine of many eukaryotic and viral proteins. The molecular structure of the ternary complex of Saccharomyces cerevisiae Nmt1p with a bound non-hydrolyzable myristoyl-CoA analog, S-(2-oxopentadecyl)-CoA, and a competitive peptidomimetic inhibitor, SC-58272, was solved to 2.9 Å resolution by X-ray crystallography. The structure determination utilized diffraction data from an iodinated ternary complex in which a newly designed and synthesized compound, S-(13-iodo-2-oxotridecyl)-CoA, was substituted for S-(2-oxopentadecyl)-CoA. Replacing the two terminal fatty acid C atoms of myristate by iodine produced, under the same crystallization conditions, heavy-atom-derivatized crystals of defined site occupancy that were isomorphous to the native complex. This approach for obtaining experimental phase information can be extended to other crystal structures of protein–fatty acyl complexes. The synthesis of S-(13-iodo-2-oxotridecyl)-CoA and the phasing procedure are described.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1107/S090744490100052X
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