Metal induced conformational changes in human insulin: crystal structures of Sr2+, Ni2+ and Cu2+ complexes of human insulin.

Crystal structures of Sr(2+), Ni(2+) and Cu(2+) of human insulin complexes have been determined. The structures of Sr(2+) and Ni(2+) complexes are similar to Zn(2+) insulin and are in T6 conformation. (All the six monomers in the insulin hexamer are in Tensed conformation (T), which means the first eight residues of B-chain are in an extended conformation).

Metal induced structural changes observed in hexameric insulin.

The metal ions in insulin hexamer play a crucial role in the T to R conformational transitions. We have determined the crystal structures of 2Mn2+, 1Rb1+ and 4Ni2+ human arg-insulin and compared them with the 2Zn2+ structure. The first two structures exist in the T3R3f state like the native 2Zn2+ arg-insulin, while the 4Ni2+ adopts a T6 conformation.

Characterization of alpha helices interacting with nucleic acids.

Protein-nucleic acid interactions play a vital role in most genetic processes. An enhanced insight into such interactions can be obtained from the structure database of these complexes. Here, we report an overall survey on the geometry of alpha helices which interact with nucleic acids through hydrogen bonds and/or non-bonded interactions.

Molecular basis of chromium insulin interactions.

The physiological role of chromium (III) in diabetes mellitus has been an area of inconclusive research for many years. It is of great interest to explore the interactions made by chromium (III) to get a better insight into their role in glucose metabolism. To understand the molecular basis of chromium action we have carried out spectroscopic and crystallographic investigations on the binding of Cr(III)-Salen with insulin, as Cr(III)-Salen is reported to result in the enhancement of insulin activity.

Structural interpretation of reduced insulin activity as seen in the crystal structure of human Arg-insulin.

The N-terminal glycine of the A-chain in insulin is reported to be one of the residues that binds to the insulin receptor. Modifications near this region lead to variations in the biological activity of insulin. One such modification viz.

A review of the hepatotoxic plant Lantana camara.

Lantana (Lantana camara Linn) is a noxious weed that grows in many tropical and subtropical parts of the world. Ingestion of lantana foliage by grazing animals causes cholestasis and hepatotoxicity. Both ruminants and nonruminant animals such as guinea pigs, rabbits, and female rats are susceptible to the hepatotoxic action of lantana toxins.

Trypsin inhibition by a peptide hormone: crystal structure of trypsin-vasopressin complex.

The large variety of serine protease inhibitors, available from various sources such as tissues, microorganisms, plants, etc., play an important role in regulating the proteolytic enzymes. The analysis of protease-inhibitor complexes helps in understanding the mechanism of action, as well as in designing inhibitors.

Secondary binding site of trypsin: revealed by crystal structure of trypsin-peptide complex.

Designed synthetic heterochiral peptides, when added to porcine trypsin, resulted in reduction of enzyme activity. The crystal structure of a complex formed between porcine trypsin and a heterochiral hepta peptide Boc-Pro-DAsp-Aib-Leu-Aib-Leu-Ala-NHMe has been determined at 1.9 A resolution.

Role of weak interactions in thermal stability of proteins.

A database analysis was done to study the role of weak interactions such as CHcdots, three dots, centeredO, CHcdots, three dots, centeredPI(m) and NHcdots, three dots, centeredPI(m) in the thermal stability of proteins. The CHcdots, three dots, centeredO and CHcdots, three dots, centeredPI(m) interactions are more in the case of thermophilic proteins as compared to mesophiles. Amino acid analysis showed that hydrophobic amino acids like Val and Ile, and Cys contribute more to CHcdots, three dots, centeredO hydrogen bonds where as Pro and Gly contribute more to CHcdots, three dots, centeredPI(m) interactions.

Hydropathy analysis to correlate structure and function of proteins.

In post-genomic era, a plethora of protein structures have been solved but the functions of some of them are unknown. In this context, the role of hydropathy index of amino acids in predicting the function of a structurally known and functionally unknown protein was explored. Initially serine protease class was taken for analysis.

Conformational switching caused by biphenyl substitution at the Calpha position: ethyl 2-benzyl-2-(formylamino)-3-phenylpropionate and ethyl 3-(1,1'-biphenyl-4-yl)-2-(formylamino)-2-(4-phenylbenzyl)propionate.

The title compounds, C19H21NO3 and C31H29NO3, are derivatives of alpha-aminoisobutyric acid, with benzyl and dibenzyl substitution. The pseudo-peptide formed by the N-formyl and ethyl ester substitution at the Calpha position switches from a trans-trans to a trans-cis configuration as a result of biphenyl substitution. The packing of the compounds is stabilized by N-H.

Trypsin activity reduced by an autocatalytically produced nonapeptide.

Trypsin, a serine protease enzyme plays a pivotal role in digestion and is autocatalytic. The crystal structure of a complex formed between porcine trypsin and an auto catalytically produced peptide is reported here. This complex shows a reduction in enzyme activity as compared to native beta-trypsin.

Crystal structure of trypsin-turkey egg white inhibitor complex.

Crystal structure of the complex between porcine beta-trypsin and the second domain of the Kazal-type ovomucoid turkey egg white trypsin inhibitor (OMTKY2) has been determined at 1.9A resolution. A peptide fragment from the first domain has been crystallized with the complex.

Precursors to dodecahedrane.

The title compounds, (2R,2"S,3b'S,4a'R,7b'S,8a'R)-perhydrodispiro[furan-2,3'-dicyclopenta[a,e]pentalene-7',2"-furan]-5,5"-dione, C(20)H(26)O(4), and (3aR,3bR,4aR,4bS,5aS,8aR,8bR,9aR,9bS,10aS)-perhydrodipentaleno[2,1-a:2',1'-e]pentalene-1,6-dione, C(20)H(26)O(2), are intermediates identified during the synthesis of dodecahedrane. Crystallographic studies have established the ring-junction stereochemistry for these important intermediates. All the ring junctions are cis-fused, and the molecular packing is stabilized by van der Waals interactions.

Ethyl 2-formamido-2-(4-iodobenzyl)-3-(4-iodophenyl)propionate and ethyl 2-(3-bromobenzyl)-3-(3-bromophenyl)-2-formamidopropionate.

The title compounds, C(19)H(19)I(2)NO(3) and C(19)H(19)Br(2)NO(3), are derivatives of alpha-aminoisobutyric acid with halogen substituents at the para and meta positions, respectively. The ethoxycarbonyl and formamide side chains attached to the C(alpha) atom of the molecule adopt extended and folded conformations, respectively. The crystal structures are stabilized by N-H.

Ethyl 6-acetylamino-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylate.

The title compound, C(20)H(21)NO(3), is a derivative of Aib (alpha-aminoisobutyric acid) and is cyclized at the C(alpha) position by biphenyl rings. The seven-membered ring possesses C2 symmetry. The C(alpha) cyclization causes the backbone to assume a helical conformation in the crystal structure.

First and unexpected synthesis of macrocyclic cyclophane-based unusual alpha-amino acid derivatives by phosphazene base without high dilution conditions.

First synthesis of a macrocylic cyclophane-based unusual alpha-amino acid derivative 11 by coupling of ethyl isocyanoacetate with 1,2-bis(4-bromomethylphenyl)ethane under phase-transfer catalysis (PTC) conditions. Phosphazene base such as 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) is useful to improve the yield of cyclophane derivative without high dilution conditions.

Structures of porcine beta-trypsin-detergent complexes: the stabilization of proteins through hydrophilic binding of polydocanol.

Polydocanol has a wide range of medical applications, especially in sclerotherapy of many diseases such as gastrointestinal antiplastia, oesophageal haemangioma etc. It is of interest to study the mode of binding of this medically important detergent and its subsequent action on proteins. Here, three crystal structures of serine protease trypsin are reported in the presence of varying concentrations of polydocanol in order to elucidate its mode of binding and interactions with proteins.

Conformational effects of C(alpha,alpha)-dipropargylglycine as a constrained residue.

A useful synthon to approach artificial phenylalanyl peptides in a [2 + 2 + 2] cycloaddition reaction, C(alpha,alpha)-dipropargylglycine (Dprg) is examined for its conformational preferences as a constrained residue. Crystal structure analysis and preliminary NMR results establish possible preference of the residue for folded (alpha) rather than extended (beta) region of the straight phi,psi conformational space. Boc-Dprg-L-Leu-OMe (1) displays two molecular conformations within the same crystallographic asymmetric unit, with Dprg in the alpha(R) or alpha(L) conformation, participating in a type I beta-turn or an alpha(L)-alpha(R)-type fold, in which Leu(2) assumes the alpha(R) conformation stereochemically favored for an L-chiral residue.

Conformational preferences of heterochiral peptides. Crystal structures of heterochiral peptides Boc-(D) Val-(D) Ala-Leu-Ala-OMe and Boc-Val-Ala-Leu-(D) Ala-OMe--enhanced stability of beta-sheet through C-H...O hydrogen bonds.

The crystal structures of Boc-(D) Val-(D) Ala-Leu-Ala-OMe (vaLA) and Boc-Val-Ala-Leu-(D) Ala-OMe (VALa) have been determined. vaLA crystallises in space group P2(1),2(1),2(1), with a = 9.401 (4), b = 17.

Purification, crystallisation and preliminary X-ray study of haemoglobin from Crocodilis palustris and Crocodilis porosus.

The unsolved three-dimensional structure of crocodile haemoglobin and its prospects as a blood substitute have led us to initiate the purification and crystallisation of haemoglobin molecules from crocodile species (Crocodilis palustris or mugger and Crocodilis porosus or salt water crocodile). The work has resulted in the prevention of polymerisation of naked haemoglobin molecules using N-ethylmaleimide or iodoacetamide. The purified monomeric haemoglobin molecule of C.

Crystal structure at 1.63 A resolution of the native form of porcine beta-trypsin: revealing an acetate ion binding site and functional water network.

The active center of a serine protease is the catalytic triad composed of His-57, Ser-195 and Asp-102. The existing crystal structure data on serine proteases have not fully answered a number of fundamental questions relating to the catalytic activity of serine proteases. The new high resolution native porcine beta-trypsin (BPT) structure is aimed at extending the knowledge on the conformation of the active site and the ordered water structure within and around the active site.

1-Isobutyl-2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-3-indoleacetic acid.

The title compound (C17H25NO3) is a perhydroindoleacetic acid which exhibits hypoglycemic activity. The cyclohexyl ring adopts a sofa conformation. The molecule contains an intramolecular O-H.

Structural basis for selective inhibition of COX-2 by nimesulide.

Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits the enzyme cyclooxygenase 2 (COX-2) more selectively than cyclooxygenase 1 (COX-1). Molecular modelling studies have been carried out on complexes of 1 with COX-1 and with mutants of COX-1 simulating COX-2. These indicate that the mutations I523V and S516A largely contribute to the selectivity.

The structure and function of antiamoebin I, a proline-rich membrane-active polypeptide.

Background: Antiamoebin is a member of the peptaibol family of polypeptides and has a unique antibiotic activity: it acts as an antiamoebic agent, but does not effectively haemolyze erythrocytes even though it does exhibit membrane-modifying activity.

Results: The structure of antiamoebin I has been determined by X-ray crystallography at 1.4 A resolution.