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Hydrogen Bonding Pattern (hydrogen + bonding_pattern)

Distribution by Scientific Domains
Chemistry75%

Selected Abstracts

Molecular docking studies of selected tricyclic and quinone derivatives on trypanothione reductase of Leishmania infantum

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 13 2010
Santhosh Kannan Venkatesan
Abstract Visceral leishmaniasis, most lethal form of Leishmaniasis, is caused by Leishmania infantum in the Old world. Current therapeutics for the disease is associated with a risk of high toxicity and development of drug resistant strains. Thiol-redox metabolism involving trypanothione and trypanothione reductase, key for survival of Leishmania, is a validated target for rational drug design. Recently published structure of trypanothione reductase (TryR) from L. infantum, in oxidized and reduced form along with Sb(III), provides vital clues on active site of the enzyme. In continuation with our attempts to identify potent inhibitors of TryR, we have modeled binding modes of selected tricyclic compounds and quinone derivatives, using AutoDock4. Here, we report a unique binding mode for quinone derivatives and 9-aminoacridine derivatives, at the FAD binding domain. A conserved hydrogen bonding pattern was observed in all these compounds with residues Thr335, Lys60, His461. With the fact that these residues aid in the orientation of FAD towards the active site forming the core of the FAD binding domain, designing selective and potent compounds that could replace FAD in vivo during the synthesis of Trypanothione reductase can be deployed as an effective strategy in designing new drugs towards Leishmaniasis. We also report the binding of Phenothiazine and 9-aminoacridine derivatives at the Z site of the protein. The biological significance and possible mode of inhibition by quinone derivatives, which binds to FAD binding domain, along with other compounds are discussed. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]

Characterization and crystal structure of D -mannitol hemihydrate

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2004
Cletus Nunes
Abstract The objectives of this study were (i) to isolate and characterize mannitol hydrate, and (ii) to solve its crystal structure from high-resolution synchrotron X-ray powder diffraction data. Mannitol hydrate was prepared by freeze-drying aqueous mannitol solutions (5% w/v) under controlled conditions. X-ray powder diffractometry, differential scanning calorimetry, and thermogravimetric analyses indicated that mannitol exists as a hemihydrate (C6H14O6,·,0.5H2O). Synchrotron data were collected on the X3B1 beamline at the National Synchrotron Light Source. The simulated annealing program PSSP was used to solve the structure, which was subsequently refined by Rietveld analysis using the program package GSAS. The compound crystallizes in space group P1, with a,=,9.8963 Å, b,=,10.5424 Å, c,=,4.7860 Å, ,,=,102.589°, ,,=,86.092°, and ,,=,116.079°. The unit cell contains two dissimilar D -mannitol molecules and one water molecule, forming a hydrogen bonding pattern significantly different from that seen in the anhydrous polymorphs. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2800,2809, 2004 [source]

X-ray and 13C solid-state NMR studies of N -benzoyl-phenylalanine

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2000
M.J. Potrzebowski
Abstract: A crystalline sample of N -benzoyl- dl -phenylalanine 1 and a polycrystalline sample of N -benzoyl- l -phenylalanine 2 were studied using 13C high-resolution solid-state NMR spectroscopy. The X-ray structure of the dl form was established. Sample 1 crystallizes in a monoclinic form with a P21/c space group, a = 11.338(1) Å, b = 9.185(1) Å, c = 14.096(2) Å, ,,= 107.53(3)°, V = 1400(3) Å3, Z = 4 and R = 0.053. The principal elements of the 13C chemical shift tensors ,ii for 1 and 2, selectively 13C (99%) labeled at the carboxyl groups were calculated. On the basis of 13C ,ii analysis the hydrogen bonding pattern for sample 2 was deduced. Enriched samples were used to establish the intermolecular distance between chemically equivalent nuclei for 1 and spatial proximity in heterogeneous domain for 2, employing the ODESSA pulse sequence. The consistence of the complementary approach covering X-ray data, analysis of the 13C ,ii parameters and ODESSA results is revealed. [source]

Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid

PROTEIN SCIENCE, Issue 2 2008
Freddie R. Salsbury Jr
Abstract Cysteine sulfenic acid (Cys-SOH), a reversible modification, is a catalytic intermediate at enzyme active sites, a sensor for oxidative stress, a regulator of some transcription factors, and a redox-signaling intermediate. This post-translational modification is not random: specific features near the cysteine control its reactivity. To identify features responsible for the propensity of cysteines to be modified to sulfenic acid, a list of 47 proteins (containing 49 known Cys-SOH sites) was compiled. Modifiable cysteines are found in proteins from most structural classes and many functional classes, but have no propensity for any one type of protein secondary structure. To identify features affecting cysteine reactivity, these sites were analyzed using both functional site profiling and electrostatic analysis. Overall, the solvent exposure of modifiable cysteines is not different from the average cysteine. The combined sequence, structure, and electrostatic approaches reveal mechanistic determinants not obvious from overall sequence comparison, including: (1) pKas of some modifiable cysteines are affected by backbone features only; (2) charged residues are underrepresented in the structure near modifiable sites; (3) threonine and other polar residues can exert a large influence on the cysteine pKa; and (4) hydrogen bonding patterns are suggested to be important. This compilation of Cys-SOH modification sites and their features provides a quantitative assessment of previous observations and a basis for further analysis and prediction of these sites. Agreement with known experimental data indicates the utility of this combined approach for identifying mechanistic determinants at protein functional sites. [source]