1AO0

GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE (PRPP) AMIDOTRANSFERASE FROM B. SUBTILIS COMPLEXED WITH ADP AND GMP

1AO0 の概要

• エントリーDOI: 10.2210/pdb1ao0/pdb
• 分子名称: GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE AMIDOTRANSFERASE, MAGNESIUM ION, IRON/SULFUR CLUSTER, ... (6 entities in total)
• 機能のキーワード: transferase, glutamine amidotransferase, prtase, purine biosynthesis, phosphoribosyltransferase, glycosyltransferase
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 204179.34

構造登録者

Tomchick, D.R.,Smith, J.L. (登録日: 1997-07-15, 公開日: 1997-11-12, 最終更新日: 2024-05-22)

主引用文献

Chen, S.,Tomchick, D.R.,Wolle, D.,Hu, P.,Smith, J.L.,Switzer, R.L.,Zalkin, H.
Mechanism of the synergistic end-product regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides.
Biochemistry, 36:10718-10726, 1997

PubMed Abstract: De novo purine nucleotide synthesis is regulated, at least in part, by end-product inhibition of glutamine PRPP amidotransferase. An important feature of this inhibition is the fact that certain synergistic nucleotide pairs give more than additive inhibition. The physiological importance of synergism is in amplifying regulation by the adenine and guanine nucleotide end products of de novo synthesis. Using a new method to quantitate synergism, ADP plus GMP were confirmed [Meyer, E., and Switzer, R. L. (1978) J. Biol. Chem. 254, 5397-5402] to give strong synergistic inhibition of Bacillus subtilis glutamine PRPP amidotransferase. An X-ray structure of the ternary enzyme.ADP.GMP complex established that ADP binds to the allosteric A site and GMP to the catalytic C site. GMP increased the binding affinity of ADP for the A site by approximately 20-fold. Synergism results from a specific nucleotide-nucleotide interaction that is dependent upon a nucleoside diphosphate in the A site and a nucleoside monophosphate in the C site. Furthermore, synergism is enhanced by the competition between nucleotide inhibitor and PRPP substrate for the C site. Purine base specificity results from a backbone carbonyl interaction of Lys305' with the 6-NH2 group of adenine in the A site and a Ser347 Ogamma interaction with the 2-NH2 group of guanine in the C site. Steric considerations favor binding of the nucleoside diphosphate to the A site. Site-directed replacements of key residues increased the nucleotide concentrations needed for 50% inhibition and in some cases perturbed synergism. Mutations in either of the nucleotide sites perturbed function at both sites, supporting the important role of synergism.

PubMed: 9271502
DOI: 10.1021/bi9711893

実験手法

X-RAY DIFFRACTION (2.8 Å)