Academic Journal
Common Mechanism of Activated Catalysis in P-loop Fold Nucleoside Triphosphatases—United in Diversity
| العنوان: | Common Mechanism of Activated Catalysis in P-loop Fold Nucleoside Triphosphatases—United in Diversity |
|---|---|
| المؤلفون: | Maria I. Kozlova, Daria N. Shalaeva, Daria V. Dibrova, Armen Y. Mulkidjanian |
| المصدر: | Biomolecules, Vol 12, Iss 10, p 1346 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Microbiology |
| مصطلحات موضوعية: | Walker ATPase, Walker A motif, Walker B motif, ATPase, Ras GTPase, ATP synthase, Microbiology, QR1-502 |
| الوصف: | To clarify the obscure hydrolysis mechanism of ubiquitous P-loop-fold nucleoside triphosphatases (Walker NTPases), we analysed the structures of 3136 catalytic sites with bound Mg-NTP complexes or their analogues. Our results are presented in two articles; here, in the second of them, we elucidated whether the Walker A and Walker B sequence motifs—common to all P-loop NTPases—could be directly involved in catalysis. We found that the hydrogen bonds (H-bonds) between the strictly conserved, Mg-coordinating Ser/Thr of the Walker A motif ([Ser/Thr]WA) and aspartate of the Walker B motif (AspWB) are particularly short (even as short as 2.4 ångströms) in the structures with bound transition state (TS) analogues. Given that a short H-bond implies parity in the pKa values of the H-bond partners, we suggest that, in response to the interactions of a P-loop NTPase with its cognate activating partner, a proton relocates from [Ser/Thr]WA to AspWB. The resulting anionic [Ser/Thr]WA alkoxide withdraws a proton from the catalytic water molecule, and the nascent hydroxyl attacks the gamma phosphate of NTP. When the gamma-phosphate breaks away, the trapped proton at AspWB passes by the Grotthuss relay via [Ser/Thr]WA to beta-phosphate and compensates for its developing negative charge that is thought to be responsible for the activation barrier of hydrolysis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 12101346 2218-273X |
| Relation: | https://www.mdpi.com/2218-273X/12/10/1346; https://doaj.org/toc/2218-273X |
| DOI: | 10.3390/biom12101346 |
| URL الوصول: | https://doaj.org/article/fd4eb8263e484062bc9e4f10ac24a55d |
| رقم الانضمام: | edsdoj.fd4eb8263e484062bc9e4f10ac24a55d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 12101346 2218273X |
|---|---|
| DOI: | 10.3390/biom12101346 |