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Journal Issue - Volume 3 Issue 6 (June 1994)

Abstract We have completed an exhaustive search for the common spatial arrangements of backbone fragments (SARFs) in nonhomologous proteins. This type of local structural similarity, incorporating short fragments of backbone atoms, arranged not necessarily in the same order along the polypeptide chain, appears to be important for protein function and stability. To estimate the statistical significance of the similarities, we have...

Abstract β‐Strands as constituents of β‐pleated sheets in protein tertiary structures often display considerable distortion from a purely extended conformation. The dislocation types are often characterized as “bulging,” “twisting,” and “bending.” The former 2 properties have been extensively studied and classified. In this work an investigation of bent β‐structures is undertaken. The structural characteristics examined included the...

Abstract To assess the respective roles of local and long‐range interactions during protein folding, the influence of the native disulfide bonds on the early formation of secondary structure was investigated using continuous‐flow circular dichroism. Within the first 4 ms of folding, lysozyme with intact disulfide bonds already had a far‐UV CD spectrum reflecting large amounts of secondary structure. Conversely, reduced lysozyme...

Abstract Protein folding conditions were established for human immunodeficiency virus integrase (IN) obtained from purified bacterial inclusion bodies. IN was denatured by 6 M guanidine · HCl–5 mM dithiothreitol, purified by gel filtration, and precipitated by ammonium sulfate. The reversible solvation of precipitated IN by 6 M guanidine · HCl allowed for wide variation of protein concentration in the folding reaction. A 6‐fold...

Abstract The crystal structure of a monoclinic form of human plasminogen kringle 4 (PGK4) has been solved by molecular replacement using the orthorhombic structure as a model and it has been refined by restrained least‐squares methods to an R factor of 16.4% at 2.25 Å resolution. The X‐PLOR structure of kringle 2 of tissue plasminogen activator (t‐PAK2) has been refined further using PROFFT (R = 14.5% at 2.38 Å resolution). The PGK4 structure...

Abstract Peptide recognition by class I products of the major histocompatibility complex requires association of the class I heavy chain with β2‐microglobulin. We present results of Monte Carlo simulations of the β‐pleated sheet floor of the human class I MHC molecule, HLA‐A2, with and without β2‐microglobulin. We find a significant effect of β2‐microglobulin on the side chains of residues near a region that would accommodate the C‐terminus of...

Abstract Hormones of the hematopoietin class mediate signal transduction by binding to specific transmembrane receptors. Structural data show that the human growth hormone (hGH) forms a complex with a homodimeric receptor and that hGH is a member of a class of hematopoietins possessing an antiparallel 4‐α‐helix bundle fold. Mutagenesis experiments suggest that electrostatic interactions may have an important influence on...

Abstract A comparison is made between a 200‐ps molecular dynamics simulation in vacuum and a normal mode analysis on the protein bovine pancreatic trypsin inhibitor (BPTI) in order to elucidate the dual aspects of harmonicity and anharmonicity in the dynamics of proteins. The molecular dynamics trajectory is analyzed using principal component analysis, an effective harmonic analysis suited for comparison with the results from the...

Abstract Using high‐sensitivity differential scanning calorimetry, we reexamined the thermodynamics of denaturation of staphylococcal nuclease. The denaturational changes in enthalpy and heat capacity were found to be functions of both temperature and pH. The denatured state of staphylococcal nuclease at pH 8.0 and high temperature has a heat capacity consistent with a fully unfolded protein completely exposed to solvent. At lower...

Abstract Staphylococcal nuclease, at low pH and in the presence of high salt concentrations, has previously been proposed to exist in a partially folded or molten globule form called the “A‐state” (Fink et al., 1993, Protein Sci 2:1155–1160). We have found that the A‐state of nuclease at pH 2.1 in the presence of moderate to high salt concentrations and at low temperature exists in a substantially folded form structurally more similar to a...

Abstract The regulatory enzyme aspartate transcarbamoylase (ATCase), comprising 2 catalytic (C) trimers and 3 regulatory (R) dimers, owes its stability to the manifold interchain interactions among the 12 polypeptide chains. With the availability of a recombinant 70‐amino acid zinc‐containing polypeptide fragment of the regulatory chain of ATCase, it has become possible to analyze directly the interaction between catalytic and...

Abstract Interaction between a 70‐amino acid and zinc‐binding polypeptide from the regulatory chain and the catalytic (C) trimer of aspartate transcarbamoylase (ATCase) leads to dramatic changes in enzyme activity and affinity for active site ligands. The hypothesis that the complex between a C trimer and 3 polypeptide fragments (zinc domain) is an analog of R state ATCase has been examined by steady‐state kinetics, heavy‐atom...

Abstract The enzyme CoA transferase (succinyl‐CoA:3‐ketoacid coenzyme A transferase [3‐oxoacid CoA transferase], EC 2.8.3.5) is essential for the metabolism of ketone bodies in the mammalian mitochondrion. It is known that its catalytic mechanism involves the transient thioesterification of an active‐site glutamate residue by CoA. As a means of identifying this glutamate within the sequence, we have made use of a fortuitous...

Abstract Neurotrophin‐3 (NT‐3) has been crystallized in 2 forms. Orthorhombic crystals, space group P21212, diffracted to 2.8 Å and have cell dimensions a = 39.1 Å, b = 54.0 Å, and c = 65.5 Å. The second form is space group P43212, with cell dimensions a = b = 67.1 Å, and c = 107.9 Å. The tetragonal crystals diffract to 2.8 Å at room temperature and 2.5 Å at −100 °C. The unit cell dimensions change significantly upon freezing, a = b = 66.1 Å, and c = 102.8...

Abstract Secondary structure prediction of the catalytic domain of matrix metalloproteinases is evaluated in the light of recently published experimentally determined structures. The prediction was made by combining conformational propensity, surface probability, and residue conservation calculated for an alignment of 19 sequences. The position of each observed secondary structure element was correctly predicted with a high degree...

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