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Science 3 June 1994:
Vol. 264. no. 5164, pp. 1427 - 1433
DOI: 10.1126/science.8197456
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Articles

Science, Vol 264, Issue 5164, 1427-1433
Copyright © 1994 by American Association for the Advancement of Science

articles

Structure of the allosteric regulatory enzyme of purine biosynthesis

JL Smith, EJ Zaluzec, JP Wery, L Niu, RL Switzer, H Zalkin, and Y Satow

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.

Multi-wavelength anomalous diffraction (MAD) has been used to determine the structure of the regulatory enzyme of de novo synthesis of purine nucleotides, glutamine 5-phosphoribosyl-1-pyrophosphate (PRPP) amidotransferase, from Bacillus subtilis. This allosteric enzyme, a 200-kilodalton tetramer, is subject to end product regulation by purine nucleotides. The metalloenzyme from B. subtilis is a paradigm for the higher eukaryotic enzymes, which have been refractory to isolation in stable form. The two folding domains of the polypeptide are correlated with functional domains for glutamine binding and for transfer of ammonia to the substrate PRPP. Eight molecules of the feedback inhibitor adenosine monophosphate (AMP) are bound to the tetrameric enzyme in two types of binding sites: the PRPP catalytic site of each subunit and an unusual regulatory site that is immediately adjacent to each active site but is between subunits. An oxygen-sensitive [4Fe-4S] cluster in each subunit is proposed to regulate protein turnover in vivo and is distant from the catalytic site. Oxygen sensitivity of the cluster is diminished by AMP, which blocks a channel through the protein to the cluster. The structure is representative of both glutamine amidotransferases and phosphoribosyltransferases.


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