Structure, dynamics, and mechanism of the lead-dependent ribozyme
Leadzyme is a small catalytic RNA that was identified by in vitro selection for Pb2+-dependent cleavage from a tRNA library. Leadzyme employs a unique two-step Pb2+-specific mechanism to cleave within its active site. NMR and crystal structures of the active site revealed different folding patterns,...
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| Format: | Article |
| Language: | English |
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De Gruyter
2011-08-01
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| Series: | Biomolecular Concepts |
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| Online Access: | https://doi.org/10.1515/bmc.2011.029 |
| _version_ | 1818587224582651904 |
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| author | Qi Xin Xia Tianbing |
| author_facet | Qi Xin Xia Tianbing |
| author_sort | Qi Xin |
| collection | DOAJ |
| description | Leadzyme is a small catalytic RNA that was identified by in vitro selection for Pb2+-dependent cleavage from a tRNA library. Leadzyme employs a unique two-step Pb2+-specific mechanism to cleave within its active site. NMR and crystal structures of the active site revealed different folding patterns, but neither features the in-line alignment for attack by the 2′-OH nucleophilic group. These experimentally determined structures most likely represent ground states and are catalytically inactive. There are significant dynamics of the active site and the motif samples multiple conformations at the ground states. Various metal ion binding sites have been identified, including one that may be occupied by a catalytic Pb2+. Based on functional group analysis, a computational model of the transition state has been proposed. This model features a unique base triple that is consistent with sequence and functional group requirements for catalysis. This structure is likely only populated transiently, but imposing appropriate conformational constraints may significantly stabilize this state thereby promoting catalysis. Other ions may inhibit the cleavage by competing for the Pb2+ binding site, or by stabilizing the ground state thereby suppressing its transition to the catalytically active conformation. Some rare earth ions can enhance the reaction via an unknown mechanism. Because of its unique chemistry and dynamic behavior, leadzyme can continue to serve as an excellent model system for teaching us RNA biology and chemistry. |
| first_indexed | 2024-12-16T09:05:28Z |
| format | Article |
| id | doaj.art-f33cf84fcfb342d2bfa14ff8f2b10135 |
| institution | Directory Open Access Journal |
| issn | 1868-5021 1868-503X |
| language | English |
| last_indexed | 2024-12-16T09:05:28Z |
| publishDate | 2011-08-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Biomolecular Concepts |
| spelling | doaj.art-f33cf84fcfb342d2bfa14ff8f2b101352022-12-21T22:37:05ZengDe GruyterBiomolecular Concepts1868-50211868-503X2011-08-012430531410.1515/bmc.2011.029Structure, dynamics, and mechanism of the lead-dependent ribozymeQi Xin0Xia Tianbing1Department of Chemistry, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USADepartment of Molecular and Cell Biology, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USALeadzyme is a small catalytic RNA that was identified by in vitro selection for Pb2+-dependent cleavage from a tRNA library. Leadzyme employs a unique two-step Pb2+-specific mechanism to cleave within its active site. NMR and crystal structures of the active site revealed different folding patterns, but neither features the in-line alignment for attack by the 2′-OH nucleophilic group. These experimentally determined structures most likely represent ground states and are catalytically inactive. There are significant dynamics of the active site and the motif samples multiple conformations at the ground states. Various metal ion binding sites have been identified, including one that may be occupied by a catalytic Pb2+. Based on functional group analysis, a computational model of the transition state has been proposed. This model features a unique base triple that is consistent with sequence and functional group requirements for catalysis. This structure is likely only populated transiently, but imposing appropriate conformational constraints may significantly stabilize this state thereby promoting catalysis. Other ions may inhibit the cleavage by competing for the Pb2+ binding site, or by stabilizing the ground state thereby suppressing its transition to the catalytically active conformation. Some rare earth ions can enhance the reaction via an unknown mechanism. Because of its unique chemistry and dynamic behavior, leadzyme can continue to serve as an excellent model system for teaching us RNA biology and chemistry.https://doi.org/10.1515/bmc.2011.029conformational constraintsconformational dynamicsleadzymemetal ion specificitytwo-step mechanism |
| spellingShingle | Qi Xin Xia Tianbing Structure, dynamics, and mechanism of the lead-dependent ribozyme Biomolecular Concepts conformational constraints conformational dynamics leadzyme metal ion specificity two-step mechanism |
| title | Structure, dynamics, and mechanism of the lead-dependent ribozyme |
| title_full | Structure, dynamics, and mechanism of the lead-dependent ribozyme |
| title_fullStr | Structure, dynamics, and mechanism of the lead-dependent ribozyme |
| title_full_unstemmed | Structure, dynamics, and mechanism of the lead-dependent ribozyme |
| title_short | Structure, dynamics, and mechanism of the lead-dependent ribozyme |
| title_sort | structure dynamics and mechanism of the lead dependent ribozyme |
| topic | conformational constraints conformational dynamics leadzyme metal ion specificity two-step mechanism |
| url | https://doi.org/10.1515/bmc.2011.029 |
| work_keys_str_mv | AT qixin structuredynamicsandmechanismoftheleaddependentribozyme AT xiatianbing structuredynamicsandmechanismoftheleaddependentribozyme |