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Ligand Uptake (ligand + uptake)

Distribution by Scientific Domains

Chemistry	75%

Selected Abstracts

Structure of relaxed-state human hemoglobin: insight into ligand uptake, transport and release

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2009
Joy D. Jenkins
Hemoglobin was one of the first protein structures to be determined by X-ray crystallography and served as a basis for the two-state MWC model for the mechanism of allosteric proteins. Since then, there has been an ongoing debate about whether Hb allostery involves the unliganded tense T state and the liganded relaxed R state or whether it involves the T state and an ensemble of liganded relaxed states. In fact, the former model is inconsistent with many functional observations, as well as the recent discoveries of several relaxed-state Hb structures such as RR2, R3 and R2. One school of thought has suggested the R2 state to be the physiologically relevant relaxed end state, with the R state mediating the T,R2 transition. X-ray studies have been performed on human carbonmonoxy Hb at a resolution of 2.8,Å. The ensuing liganded quaternary structure is different from previously reported liganded Hb structures. The distal ,-heme pocket is the largest when compared with other liganded Hb structures, partly owing to rotation of ,His63(E7) out of the distal pocket, creating a ligand channel to the solvent. The structure also shows unusually smaller ,- and ,-clefts. Results from this study taken in conjunction with previous findings suggest that multiple liganded Hb states with different quaternary structures may be involved in ligand uptake, stabilization, transport and release. [source]

The clinical and neuroimaging studies in Holmes tremor

ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2010
A. Gajos
Gajos A, Bogucki A, Schinwelski M, So,tan W, Rudzi,ska M, Budrewicz S, Koszewicz M, Majos A, Górska-Chrz,stek M, Bie,kiewicz M, Ku,mierek J, S,awek J. The clinical and neuroimaging studies in Holmes tremor. Acta Neurol Scand: 2010: 122: 360,366. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Aim,,, Holmes tremor (HT) is a combination of rest, postural and action tremor. A parallel dysfunction of cerebello-thalamic and nigrostriatal pathways seems necessary to produce this kind of tremor. We present the clinical and neuroimaging study verifying that hypothesis. Material and methods,,, A total of 10 patients: five male, five female, fulfilling consensus criteria were included. Demographic, clinical and neuroimaging data (MRI = 9; CT = 1, SPECT with the use of 123-I-FP CIT: DaTSCAN in six patients to assess the presynaptic dopaminergic nigrostriatal system involvement, indices of asymmetry for ligand uptake for each striatum were calculated) were analyzed. Results,,, Hemorrhage was the most frequent etiology and thalamus , the most commonly involved structure. Contrary to the previous reports, the visual assessment did not reveal remarkable interhemispheric differences of DaTSCAN uptake. Quantitative measurements showed only minimal differences. Conclusions,,, It is open to debate whether nigrostriatal pathway damage is crucial for the phenomenology of HT. Alternative hypothesis is presented that HT represents the heterogeneous spectrum of tremors with similar phenomenology, but different pathophysiology. [source]

Site-Specific Investigation of the Steady-State Kinetics and Dynamics of the Multistep Binding of Bile Acid Molecules to a Lipid Carrier Protein

CHEMISTRY - A EUROPEAN JOURNAL, Issue 37 2010
Dr. Clelia Cogliati
Abstract The investigation of multi-site ligand,protein binding and multi-step mechanisms is highly demanding. In this work, advanced NMR methodologies such as 2D 1H,15N line-shape analysis, which allows a reliable investigation of ligand binding occurring on micro- to millisecond timescales, have been extended to model a two-step binding mechanism. The molecular recognition and complex uptake mechanism of two bile salt molecules by lipid carriers is an interesting example that shows that protein dynamics has the potential to modulate the macromolecule,ligand encounter. Kinetic analysis supports a conformational selection model as the initial recognition process in which the dynamics observed in the apo form is essential for ligand uptake, leading to conformations with improved access to the binding cavity. Subsequent multi-step events could be modelled, for several residues, with a two-step binding mechanism. The protein in the ligand-bound state still exhibits a conformational rearrangement that occurs on a very slow timescale, as observed for other proteins of the family. A global mechanism suggesting how bile acids access the macromolecular cavity is thus proposed. [source]