The Permian System in Kansas

Rocks of Permian age in Kansas were first recognized in 1895, and by the early 21st century the internationally accepted boundary between the Permian and the Carboniferous (Pennsylvanian Subsystem) was recognized in Kansas at the base of the Bennett Shale Member of the Red Eagle Limestone. The upper boundary of the Permian is an erosional unconformity that is overlain by rocks of Cretaceous age. Currently accepted stratigraphic nomenclature for the Permian of Kansas recognizes the Wolfcampian, Leonardian, and Guadalupian Series, and the lithostratigraphic formations within each of these series reflect a wide spectrum of depositional environments. Summaries of the lithofacies, thicknesses, depositional environments, and source areas of, and for, the rocks in each series provide a basis for inferring the history of the Permian in Kansas as currently understood. Fluctuations from shallow-marine to terrestrial environments associated with climate change as a result of the waning of Gondwana glaciers and latitudinal shifts are recorded in the Permian rocks of Kansas. Economically these Permian rocks have been, and are, an important source of hydrocarbons, salt, gypsum, building stone, aggregate, and ground water. This report on the Permian System in Kansas is "a work in progress" and future multi-disciplinary studies of chrono- and sequence stratigraphy, climate history, structural aspects, sediment transport, and diagenesis will further enhance our understanding of the end of the Paleozoic in Kansas. Cover photo--The broad, flat surface in the center of the photo is the top of the Glenrock Limestone Member of the Red Eagle Limestone and the Carboniferous-Permian boundary at Tuttle Creek Lake Spillway in Pottawatomie County, Kansas

The Permian System in Kansas

Rocks of Permian age in Kansas were first recognized in 1895, and by the early 21st century the internationally accepted boundary between the Permian and the Carboniferous (Pennsylvanian Subsystem) was recognized in Kansas at the base of the Bennett Shale Member of the Red Eagle Limestone. The upper boundary of the Permian is an erosional unconformity that is overlain by rocks of Cretaceous age. Currently accepted stratigraphic nomenclature for the Permian of Kansas recognizes the Wolfcampian, Leonardian, and Guadalupian Series, and the lithostratigraphic formations within each of these series reflect a wide spectrum of depositional environments. Summaries of the lithofacies, thicknesses, depositional environments, and source areas of, and for, the rocks in each series provide a basis for inferring the history of the Permian in Kansas as currently understood. Fluctuations from shallow-marine to terrestrial environments associated with climate change as a result of the waning of Gondwana glaciers and latitudinal shifts are recorded in the Permian rocks of Kansas. Economically these Permian rocks have been, and are, an important source of hydrocarbons, salt, gypsum, building stone, aggregate, and ground water. This report on the Permian System in Kansas is "a work in progress" and future multi-disciplinary studies of chrono- and sequence stratigraphy, climate history, structural aspects, sediment transport, and diagenesis will further enhance our understanding of the end of the Paleozoic in Kansas. Cover photo--The broad, flat surface in the center of the photo is the top of the Glenrock Limestone Member of the Red Eagle Limestone and the Carboniferous-Permian boundary at Tuttle Creek Lake Spillway in Pottawatomie County, Kansas

Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain

Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro

Loop Interactions during Catalysis by Dihydrofolate Reductase fromMoritella profunda

Dihydrofolate reductase (DHFR) is often used as a model system to study the relation between protein dynamics and catalysis. We have studied a number of variants of the cold-adapted DHFR from Moritella profunda (MpDHFR), in which the catalytically important M20 and FG loops have been altered, and present a comparison with the corresponding variants of the wellstudied DHFR from Escherichia coli (EcDHFR). Mutations in the M20 loop do not affect the actual chemical step of transfer of hydride from reduced nicotinamide adenine dinucleotide phosphate to the substrate 7,8-dihydrofolate in the catalytic cycle in either enzyme; they affect the steady state turnover rate in EcDHFR but not in MpDHFR. Mutations in the FG loop also have different effects on catalysis by the two DHFRs. Despite the two enzymes most likely sharing a common catalytic cycle at pH 7, motions of these loops, known to be important for progression through the catalytic cycle in EcDHFR, appear not to play a significant role in MpDHFR

Hydride transfer catalysed by Escherichia coli and Bacillus subtilis dihydrofolate reductase: coupled motions and distal mutations

This paper reviews the results from hybrid quantum/classical molecular dynamics simulations of the hydride transfer reaction catalysed by wild-type (WT) and mutant Escherichia coli and WT Bacillus subtilis dihydrofolate reductase (DHFR). Nuclear quantum effects such as zero point energy and hydrogen tunnelling are significant in these reactions and substantially decrease the free energy barrier. The donor–acceptor distance decreases to ca 2.7 Å at transition-state configurations to enable the hydride transfer. A network of coupled motions representing conformational changes along the collective reaction coordinate facilitates the hydride transfer reaction by decreasing the donor–acceptor distance and providing a favourable geometric and electrostatic environment. Recent single-molecule experiments confirm that at least some of these thermally averaged equilibrium conformational changes occur on the millisecond time-scale of the hydride transfer. Distal mutations can lead to non-local structural changes and significantly impact the probability of sampling configurations conducive to the hydride transfer, thereby altering the free-energy barrier and the rate of hydride transfer. E. coli and B. subtilis DHFR enzymes, which have similar tertiary structures and hydride transfer rates with 44% sequence identity, exhibit both similarities and differences in the equilibrium motions and conformational changes correlated to hydride transfer, suggesting a balance of conservation and flexibility across species

Apostles in the New Testament

Thesis (M.A.) -- University of Stellenbosch, 1977.One copy microfiche.Full text to be digitised and attached to bibliographic record