Structure and dynamics of a molten globular enzyme.

@article{citeulike:2034738, abstract = {Although protein dynamics has been recognized as a potentially important contributor to enzyme catalysis, structural disorder is generally considered to reduce catalytic efficiency. This widely held assumption has recently been challenged by the finding that an engineered chorismate mutase combines high catalytic activity with the properties of a molten globule, a loosely packed and highly dynamic conformational ensemble. Taking advantage of the ordering observed upon ligand binding, we have now used NMR spectroscopy to characterize this enzyme in complex with a transition-state analog. The complex adopts a helix-bundle structure, as designed, but retains unprecedented flexibility on the millisecond timescale across its entire length. Moreover, pre-steady-state kinetics data show that binding occurs by an induced-fit mechanism on the same timescale as the enzymatic reaction, linking global conformational plasticity with efficient catalysis.}, address = {[1] Laboratory of Physical Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland [2] Present address: School of Biological Sciences, Nanyang Technological University, 60, Nanyang Drive, Singapore 637551, Singapore.}, author = {Pervushin, Konstantin and Vamvaca, Katherina and V\"{o}geli, Beat and Hilvert, Donald }, citeulike-article-id = {2034738}, doi = {10.1038/nsmb1325}, issn = {1545-9993}, journal = {Nat Struct Mol Biol}, keywords = {binding, clip2, enzyme, experiment, intrinsic\_disorder, ligand, molten\_globule, nmr}, month = {November}, posted-at = {2008-01-15 07:17:14}, priority = {2}, title = {Structure and dynamics of a molten globular enzyme.}, url = {http://dx.doi.org/10.1038/nsmb1325}, year = {2007} }

TY - JOUR ID - citeulike:2034738 L3 - citeulike-article-id:2034738 TI - Structure and dynamics of a molten globular enzyme. JF - Nat Struct Mol Biol AD - [1] Laboratory of Physical Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland [2] Present address: School of Biological Sciences, Nanyang Technological University, 60, Nanyang Drive, Singapore 637551, Singapore. SN - 1545-9993 N2 - Although protein dynamics has been recognized as a potentially important contributor to enzyme catalysis, structural disorder is generally considered to reduce catalytic efficiency. This widely held assumption has recently been challenged by the finding that an engineered chorismate mutase combines high catalytic activity with the properties of a molten globule, a loosely packed and highly dynamic conformational ensemble. Taking advantage of the ordering observed upon ligand binding, we have now used NMR spectroscopy to characterize this enzyme in complex with a transition-state analog. The complex adopts a helix-bundle structure, as designed, but retains unprecedented flexibility on the millisecond timescale across its entire length. Moreover, pre-steady-state kinetics data show that binding occurs by an induced-fit mechanism on the same timescale as the enzymatic reaction, linking global conformational plasticity with efficient catalysis. KW - binding KW - clip2 KW - enzyme KW - experiment KW - intrinsic_disorder KW - ligand KW - molten_globule KW - nmr AU - Pervushin, Konstantin AU - Vamvaca, Katherina AU - Vögeli, Beat AU - Hilvert, Donald PY - 2007/11/11/ UR - http://dx.doi.org/10.1038/nsmb1325 ER -