Conformation Similar (conformation + similar)

Distribution by Scientific Domains
Distribution within Chemistry


Selected Abstracts


Biochemical characteristics of C-terminal region of recombinant chitinase from Bacillus licheniformis, implication of necessity for enzyme properties

FEBS JOURNAL, Issue 9 2008
Hsu-Han Chuang
The functional and structural significance of the C-terminal region of Bacillus licheniformis chitinase was explored using C-terminal truncation mutagenesis. Comparative studies between full-length and truncated mutant molecules included initial rate kinetics, fluorescence and CD spectrometric properties, substrate binding and hydrolysis abilities, thermostability, and thermodenaturation kinetics. Kinetic analyses revealed that the overall catalytic efficiency, kcat/Km, was slightly increased for the truncated enzymes toward the soluble 4-methylumbelliferyl- N-N,-diacetyl chitobiose or 4-methylumbelliferyl- N - N,- N,-triacetyl chitotriose or insoluble ,-chitin substrate. By contrast, changes to substrate affinity, Km, and turnover rate, kcat, varied considerably for both types of chitin substrates between the full-length and truncated enzymes. Both truncated enzymes exhibited significantly higher thermostabilities than the full-length enzyme. The truncated mutants retained similar substrate-binding specificities and abilities against the insoluble substrate but only had approximately 75% of the hydrolyzing efficiency of the full-length chitinase molecule. Fluorescence spectroscopy indicated that both C-terminal deletion mutants retained an active folding conformation similar to the full-length enzyme. However, a CD melting unfolding study was able to distinguish between the full-length and truncated mutant molecules by the two phases of apparent transition temperatures in the mutants. These results indicate that up to 145 amino acid residues, including the putative C-terminal chitin-binding region and the fibronectin (III) motif of B. licheniformis chitinase, could be removed without causing a seriously aberrant change in structure and a dramatic decrease in insoluble chitin hydrolysis. The results of the present study provide evidence demonstrating that the binding and hydrolyzing of insoluble chitin substrate for B. licheniformis chitinase was not dependent solely on the putative C-terminal chitin-binding region and the fibronectin (III) motif. [source]


Neuroserpin Portland (Ser52Arg) is trapped as an inactive intermediate that rapidly forms polymers

FEBS JOURNAL, Issue 16 2004
Implications for the epilepsy seen in the dementia FENIB
The dementia familial encephalopathy with neuroserpin inclusion bodies (FENIB) is caused by point mutations in the neuroserpin gene. We have shown a correlation between the predicted effect of the mutation and the number of intracerebral inclusions, and an inverse relationship with the age of onset of disease. Our previous work has shown that the intraneuronal inclusions in FENIB result from the sequential interaction between the reactive centre loop of one neuroserpin molecule with ,-sheet A of the next. We show here that neuroserpin Portland (Ser52Arg), which causes a severe form of FENIB, also forms loop-sheet polymers but at a faster rate, in keeping with the more severe clinical phenotype. The Portland mutant has a normal unfolding transition in urea and a normal melting temperature but is inactive as a proteinase inhibitor. This results in part from the reactive loop being in a less accessible conformation to bind to the target enzyme, tissue plasminogen activator. These results, with those of the CD analysis, are in keeping with the reactive centre loop of neuroserpin Portland being partially inserted into ,-sheet A to adopt a conformation similar to an intermediate on the polymerization pathway. Our data provide an explanation for the number of inclusions and the severity of dementia in FENIB associated with neuroserpin Portland. Moreover the inactivity of the mutant may result in uncontrolled activity of tissue plasminogen activator, and so explain the epileptic seizures seen in individuals with more severe forms of the disease. [source]


Structure of a mutant T = 1 capsid of Sesbania mosaic virus: role of water molecules in capsid architecture and integrity

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 10 2005
V. Sangita
Deletion of the N-terminal 31 amino acids from the coat protein (CP) of Sesbania mosaic virus (SeMV) results in the formation of T = 1 capsids. The X-ray crystal structure of CP-N,31 mutant capsids reveals that the CP adopts a conformation similar to those of other T = 1 mutants. The 40 N-terminal residues are disordered in CP-N,31. The intersubunit hydrogen bonds closely resemble those of the native capsid. The role of water molecules in the SeMV structure has been analyzed for the first time using the present structure. As many as 139 of the 173 waters per subunit make direct contacts with the protein atoms. The water molecules form a robust scaffold around the capsid, stabilize the loops and provide integrity to the subunit. These waters constitute a network connecting diametrically opposite ends of the subunit. Such waters might act as nodes for conveying signals for assembly or disassembly across a large conformational space. Many water-mediated interactions are observed at various interfaces. The twofold interface, which has the smallest number of protein,protein contacts, is primarily held by water-mediated interactions. The present structure illuminates the role of water molecules in the structure and stability of the capsid and points out their possible significance in assembly. [source]


Crystal structure of achiral nonapeptide Boc,(Aib,,zPhe)4,Aib,OMe at atomic resolution: Evidence for a 310 -helix

BIOPOLYMERS, Issue 3 2003
Yoshihito Inai
Abstract An x-ray crystallographic analysis was carried out for Boc,(Aib,,ZPhe)4,Aib,OMe (1: Boc = t -butoxycarbonyl; Aib = ,-aminoisobutyric acid; ,ZPhe = Z -,,,-didehydrophenylalanine) to provide the precise conformational parameters of the octapeptide segment ,(Aib,,ZPhe)4,. Peptide 1 adopted a typical 310 -helical conformation characterized by ,,, = 55.8 (50,65), ,,, = 26.7 (15,45), and ,,, = 179.5 (168,188) for the average values of the ,(Aib,,ZPhe)4, segment (the range of the eight values). The 310 -helix contains 3.1 residues per turn, being close to the "perfect 310 -helix" characterized by 3.0 residues per turn. NMR and Fourier transform infrared (FTIR) spectroscopy revealed that the 310 -helical conformation at the atomic resolution is essentially maintained in solution. Energy minimization of peptide 1 by semiempirical molecular orbital calculation converged to a 310 -helical conformation similar to the x-ray crystallographic 310 -helix. The preference for a 310 -helix in the ,(Aib,,ZPhe)4, segment is ascribed to strong inducers of the 310 -helix inherent in Aib and ,ZPhe residues,in particular, the Aib residues tend to stabilize a 310 -helix more effectively. Therefore, the ,(Aib,,ZPhe)4, segment is useful to rationally design an optically inactive 310 -helical backbone, which will be of great importance to provide novel insights into noncovalent and covalent chiral interactions of a helical peptide with a chiral molecule. 2003 Wiley Periodicals, Inc. Biopolymers 70: 310,322, 2003 [source]


Protein,protein docking with multiple residue conformations and residue substitutions

PROTEIN SCIENCE, Issue 6 2002
David M. Lorber
Abstract The protein docking problem has two major aspects: sampling conformations and orientations, and scoring them for fit. To investigate the extent to which the protein docking problem may be attributed to the sampling of ligand side-chain conformations, multiple conformations of multiple residues were calculated for the uncomplexed (unbound) structures of protein ligands. These ligand conformations were docked into both the complexed (bound) and unbound conformations of the cognate receptors, and their energies were evaluated using an atomistic potential function. The following questions were considered: (1) does the ensemble of precalculated ligand conformations contain a structure similar to the bound form of the ligand? (2) Can the large number of conformations that are calculated be efficiently docked into the receptors? (3) Can near-native complexes be distinguished from non-native complexes? Results from seven test systems suggest that the precalculated ensembles do include side-chain conformations similar to those adopted in the experimental complexes. By assuming additivity among the side chains, the ensemble can be docked in less than 12 h on a desktop computer. These multiconformer dockings produce near-native complexes and also non-native complexes. When docked against the bound conformations of the receptors, the near-native complexes of the unbound ligand were always distinguishable from the non-native complexes. When docked against the unbound conformations of the receptors, the near-native dockings could usually, but not always, be distinguished from the non-native complexes. In every case, docking the unbound ligands with flexible side chains led to better energies and a better distinction between near-native and non-native fits. An extension of this algorithm allowed for docking multiple residue substitutions (mutants) in addition to multiple conformations. The rankings of the docked mutant proteins correlated with experimental binding affinities. These results suggest that sampling multiple residue conformations and residue substitutions of the unbound ligand contributes to, but does not fully provide, a solution to the protein docking problem. Conformational sampling allows a classical atomistic scoring function to be used; such a function may contribute to better selectivity between near-native and non-native complexes. Allowing for receptor flexibility may further extend these results. [source]


Halide salts of antimigraine agents eletriptan and naratriptan

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 12 2008
K. Ravikumar
Molecules of eletriptan hydrobromide monohydrate (systematic name: (1S,2R)-1-methyl-2-{5-[2-(phenylsulfonyl)ethyl]-1H -indol-3-ylmethyl}pyrrolidinium bromide monohydrate), C22H27N2O2S+Br,H2O, (I), and naratriptan hydrochloride (systematic name: 1-methyl-4-{5-[2-(methylsulfamoyl)ethyl]-1H -indol-3-yl}piperidinium chloride), C17H26N3O2S+Cl,, (II), adopt conformations similar to other triptans. The C-2 and C-5 substituents of the indole ring, both of which are in a region of conformational flexibility, are found to be oriented on either side of the indole ring plane in (I), whilst they are on the same side in (II). The N atom in the C-2 side chain is protonated in both structures and is involved in the hydrogen-bonding networks. In (I), the water molecules create helical hydrogen-bonded chains along the c axis. In (II), the hydrogen bonding of the chloride ions results in macrocyclic R42(20) and R42(24) ring motifs that form sheets in the bc plane. This structural analysis provides an insight into the molecular structure,activity relationships within this class of compound, which is of use for drug development. [source]