ISSN:
0091-7419
Keywords:
Life Sciences
;
Molecular Cell Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
The three-dimensional structure of the multisubunit allosteric enzyme, aspartate transcarbamylase, has been determined to 5.5 Å resolution. An unusual feature of the molecule is a large central aqueous cavity 50 Å × 50 Å × 25 Å, into which the active sites face. Access to the central cavity and the active site region is provided by six equivalent channels of 15 Å diameter.A complex C6R4, composed of catalytic trimers C3 and of regulatory dimers R2, has been isolated upon treatment of aspartate transcarbamylase (ATCase, C6R6) by mercurials. The specific catalytic activity of C6R4 is essentially the same as that of ATCase, about 70% of that of the catalytic trimers at 30 mM aspartate and saturating carbamyl phosphate. Allosteric interactions are reduced in C6R4 as compared with those in ATCase. In the homotropic interactions the Hill coefficient is reduced from approximately 3.3 to 2.1 at pH 8.3, while the heterotropic interactions of both cytidine triphosphate (CTP) and adenosine triphosphate (ATP) are reduced substantially but not abolished at pH 8.3. Thus, the allosteric transitions involved in the regulatory mechanisms do not require the intact structure C6R6. Also, this regulation is not simply the control of access of substrates or products to or from the large central aqueous cavity in the ATCase molecule.Comparison of electron density maps at 5.5 Å resolution for ATCase and for the complex of ATCase with CTP shows substantial similarities throughout the three-dimensional electron density maps. Significant differences are seen, however, in the region of the regulatory dimers R2 where CTP adds, and near the active sites in the catalytic trimers C3.
Additional Material:
16 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jss.400020203
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