Conformational dynamics associated with ligand binding to vertebrate hexa-coordinate hemoglobins

Neuroglobin (Ngb) and cytoglobin (Cygb) are two new additions to the globin family, exhibiting heme iron hexa-coordination, a disulfide bond and large internal cavities. These proteins are implicated in cytoprotection under hypoxic-ischemic conditions, but the molecular basis of their cytoprotective function is unclear. Herein, a photothermal and spectroscopic study of the interactions of diatomic ligands with Ngb, Cygb, myoglobin and hemoglobin is presented. The impact of the disulfide bond in Ngb and Cygb and role of conserved residues in Ngb His64, Val68, Cys55, Cys120 and Tyr44 on conformational dynamics associated with ligand binding/dissociation were investigated. Transient absorption and photoacoustic calorimetry studies indicate that CO photo-dissociation from Ngb leads to a volume expansion (13.4±0.9 mL mol-1), whereas a smaller volume change was determined for Ngb with reduced Cys (ΔV=4.6±0.3 mL mol-1). Furthermore, Val68 side chain regulates ligand migration between the distal pocket and internal hydrophobic cavities since Val68Phe geminate quantum yield is ∼2.7 times larger than that of WT Ngb. His64Gln and Tyr44Phe mutations alter the thermodynamic parameters associated with CO photo-release indicating that electrostatic/hydrogen binding network that includes heme propionate groups, Lys 67, His64, and Tyr 44 in Ngb modulates the energetics of CO photo-dissociation. In Cygb, CO escape from the protein matrix is fast (< 40 ns) with a ΔH of 18±2 kcal mol-1 in Cygbred, whereas disulfide bridge formation promotes a biphasic ligand escape associated with an overall enthalpy change of 9±4 kcal mol-1. Therefore, the disulfide bond modulates conformational dynamics in Ngb and Cygb. I propose that in Cygb with reduced Cys the photo-dissociated ligand escapes through the hydrophobic tunnel as occurs in Ngb, whereas the CO preferentially migrates through the His64 gate in Cygbox. To characterize Cygb surface 1,8-ANS interactions with Cygb were investigated employing fluorescence spectroscopy, ITC and docking simulations. Two 1,8-ANS binding sites were identified. One binding site is located close to the extended N-terminus of Cygb and was also identified as a binding site for oleate. Furthermore, guanidinium hydrochloride-induced unfolding studies of Cygb reveal that the disulfide bond does not impact Cygb stability, whereas binding of cyanide slightly increases the protein stability.

Molecular mechanics application in inorganic Chemistry

The present paper is a review about basic principles of the molecular mechanics that is the most important tool used in molecular modeling area, and their applications to the calculation of the relative stability and chemical reactivity of organometalic and coordination compounds. We show how molecular mechanics can be successfully applied to a wide variety of inorganic systems.

(Appendix) Bulk inorganic chemistry at DSDP Leg 77 Holes

Clay mineralogic and inorganic geochemical investigations of Cretaceous and Cenozoic sediments of the western Gulf of Mexico lead to the following main conclusions. (1) Transition of lowermost Cretaceous continental to marine sedimentation is marked by a clay evaporitic stage, north of the Campeche Escarpment. (2) Existence of combined mineralogic and geochemical stratigraphy allows us to propose correlations between Sites 535 and 540, especially for the Albian. (3) Predominance of detrital clay assemblages is indicative of hot and variably humid continental climate until the early late Cenozoic. (4) Tectonic destabilization of the margins of Gulf of Mexico occurred at different periods, especially until the middle Cretaceous, with a mixed erosion of rocks and soils and temporary oxidized conditions of deposition. (5) Successive developments of confined perimarine basins occurred from the earliest Cretaceous until the Miocene, chiefly in the Florida area. The sources of inorganic materials were chiefly situated on the east of the studied area until the late Tertiary and after that in the Mississippi River basin. (6) Occasionally, volcanic activity influenced the clay mineralogy and mainly the geochemistry, and possibly contributed to the rather strong magnesian character of the deposition until the late Paleogene. (7) The argillaceous diagenesis is weak; variability of the carbonate diagenesis is marked by the relation Sr = f(CaO) and chiefly depends on the depth of burial, the clay content, the porosity, and the geologic age.

smith's inorganic chemistry,

Mode of access: Internet.

Comprehensive inorganic chemistry

Bibliographical footnotes.

Inorganic chemistry syallabus /

Used in the "freshman classes of the Department of Medicine, University of Minnesota"--P. [7].

A text-book of inorganic chemistry,

Mode of access: Internet.

Problems in inorganic chemistry,

Mode of access: Internet.

Modern inorganic chemistry /

Includes index.

A course in inorganic chemistry for colleges,

Table on end-paper.

The principles of inorganic chemistry;

Mode of access: Internet.

Introduction to general inorganic chemistry,

Mode of access: Internet.

Recent advances in physical and inorganic chemistry;

Mode of access: Internet.

Inorganic chemistry,

Mode of access: Internet.

A text-book of inorganic chemistry,

Includes bibliographical references.