Use of a vinyl phosphonate analog of ATP as a rotationally constrained probe of the C5′---O5′ torsion angle in ATP complexed to methionine adenosyl transferase |
| |
Authors: | Francis Kappler Ton T Hai Alexander Hampton |
| |
Institution: | Institute for Cancer Research, The Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 USA |
| |
Abstract: | An analog of adenosine 5′-triphosphate (ATP) was synthesized in which the C4′---C5′---O---Pα system is replaced by a trans C4′---CH=CH---Pα system. In the form of 1:1 complexes with Mg, this analog and its counterpart with a C4′---CH2---CH2---Pα system were linear competitive inhibitors, with respect to MgATP, of the MAT-II (normal tissue) and MAT-T (hepatoma tissue) forms of rat ATP:
-methionine-S-adenosyltransferase (MAT); Km(ATP)/Ki values ranged from 0.4 to 2.4. 2′-Deoxy-ATP was a weak substrate, Km(ATP)/Km = 0.035, of MAT-II and a weak competitive inhibitor, Km(ATP)/Ki = 0.07, of MAT-T. These findings, together with interactions of the MAT forms with other substrates and inhibitors, indicate that binding of ATP to these transferases is accompanied by little rotation about the C5′---O5′ bond, and that C4′ and Pα are in a trans-type relationship in enzyme-bound ATP. |
| |
Keywords: | Author to whom correspondence should be addressed |
本文献已被 ScienceDirect 等数据库收录! |
|