Structure–function relationships in proteins are predicated on the spatial proximity of noncovalently interacting groups atoms. Thus, structural elements located away from a protein's active site typically presumed to serve stabilizing or scaffolding role for larger structure. Here we report functional distal element PDZ domain, even though it is not required maintain The third domain PSD-95/SAP90 (PDZ3) has an unusual additional alpha helix (α3) that packs contiguous fashion against...

Allostery in proteins influences various biological processes such as regulation of gene transcription and activities enzymes cell signaling. Computational approaches for analysis allosteric coupling provide inexpensive opportunities to predict mutations design small-molecule agents control protein function cellular activity. We develop a computationally efficient network-based method, Ohm, identify characterize communication networks within proteins. Unlike previously developed...

Cryptochromes are blue-light photoreceptors that regulate a variety of responses such as growth and circadian rhythms in organisms ranging from bacteria to humans. share high level sequence identity with the light-activated DNA repair enzyme photolyase. Photolyase uses energy blue light UV-induced photoproducts through cyclic electron transfer between catalytic flavin adenine dinucleotide cofactor damaged DNA. lack activity, their mechanism signal transduction is not known. It hypothesized...

Long-range intraprotein interactions give rise to many important protein behaviors. Understanding how energy is transduced through structures either transmit a signal or elicit conformational changes therefore current challenge in structural biology. In an effort understand such linkages, multiple V → A mutations were made the small globular eglin c. The physical responses, as mapped by NMR spin relaxation, residual dipolar couplings (RDCs), and scalar couplings, illustrate that interior of...

Increases in peak capacity that are achieved using comprehensive rather than single-column gas chromatography also often accompanied by significant improvements minimum detectable amounts. Comprehensive utilizes a zone compression of eluent between primary and secondary columns, with complete conservation mass. In this paper, we present theoretical model amplitude enhancement based on translation the fractional area under column normal curve to Gaussian peak. Amplitude made modulation scales...

A reverse epidemiology of classic cardiovascular risk factors was observed in hemodialysis patients with a high comorbidity burden. We hypothesized that uric acid, novel factor, also has an altered association survival these patients.A retrospective study conducted on 168 consecutive outpatient over 6-year period. Serum albumin levels and relevant laboratory information were recorded monthly. The disease severity assessed using Comorbidity Index (CoI) scores. Patients stratified into 3...

PDZ (PSD95/Discs large/ZO-1) domains are ubiquitous protein interaction motifs found in scaffolding proteins involved signal transduction. Despite the fact that many show a limited tendency to undergo structural change, family has been associated with long-range communication and allostery. One of studied most terms structure biophysical properties is second ("PDZ2") domain from tyrosine phosphatase 1E (PTP1E, also known as PTPL1). Previously, we showed through NMR relaxation studies binding...

A comparison of 2H- and 13C-based NMR relaxation methods to characterize the dynamics methyl groups in proteins is presented. Using human ubiquitin as a model system, field dependence carbon deuterium parameters has been measured used probe utility various forms model-free formalism revealing underlying dynamics. We find that both approaches reveal same overall dynamical features provided suitable parametrization spectral densities are employed. It found original extended formalisms yield...

The temperature dependence of the fast internal dynamics calcium-saturated calmodulin in complex with a peptide corresponding to calmodulin-binding domain smooth muscle myosin light chain kinase is examined using 15N and 2H NMR relaxation methods. studies were carried out at 13 temperatures that span 288−346 K. backbone over four dozen methyl-bearing side chains, distributed throughout molecule, probed. chains show much more variable often considerably larger response than backbone. A...

Long-range interactions are fundamental to protein behaviors such as cooperativity and allostery. In an attempt understand the role flexibility plays in interactions, distribution of local fluctuations a globular was monitored response localized, nonelectrostatic perturbations. Two valine-to-alanine mutations were introduced into small serine protease inhibitor eglin c, 15N 2H NMR spin relaxation properties these variants analyzed terms Lipari−Szabo dynamics formalism compared those wild...

To characterize the long-range structure that persists in unfolded form of 70-residue protein eglin C, residual dipolar couplings (RDCs) for HN-N and HA-CA bond vectors were measured by NMR spectroscopy both its low pH, urea denatured state native state. When data sets two different structural states compared, a statistically significant correlation was found, with yielding coefficient r = 0.47 to 0.51. This finding directly demonstrates C has nativelike global structure, conclusion reached...

Optogenetics is a technique for establishing direct spatiotemporal control over molecular function within living cells using light. Light application induces conformational changes targeted proteins that produce in function. One of the applications optogenetic tools an allosteric via light-sensing domain (LOV2), which allows and robust protein Computational studies supported by cellular imaging demonstrated light allosterically inhibited signaling Vav2, ITSN, Rac1, but structural dynamic...