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Journal Issue - Volume 10 Issue 8 (August 2001)

  • Thank you John Collier!

  • Mark Hermodson
  • Published in Wiley Interscience on Dec 31, 2008
  • DOI: 10.1002/pro.101479 (p 1479-1479)

Abstract Cyclic nucleotide phosphodiesterase 3A (PDE3A) hydrolyzes cAMP to AMP, but is competitively inhibited by cGMP due to a low kcat despite a tight Km. Cyclic AMP elevation is known to inhibit all pathways of platelet activation, and thus regulation of PDE3 activity is significant. Although cGMP elevation will inhibit platelet function, the major action of cGMP in platelets is to elevate cAMP by inhibiting PDE3A. To investigate...

Abstract Human liver cytosolic (ALDH1) and mitochondrial (ALDH2) aldehyde dehydrogenases are both encoded in the nucleus and synthesized in the cytosol. ALDH1 must fold in the cytosol, but ALDH2 is first synthesized as a precursor and must remain unfolded during import into mitochondria. The two mature forms share high identity (68%) at the protein sequence level except for the first 21 residues (14%); their tertiary structures were...

Abstract The design of safe sweeteners is very important for people who are affected by diabetes, hyperlipemia, and caries and other diseases that are linked to the consumption of sugars. Sweet proteins, which are found in several tropical plants, are many times sweeter than sucrose on a molar basis. A good understanding of their structure–function relationship can complement traditional SAR studies on small molecular weight...

Abstract Streptomyces venezuelae synthesizes chloramphenicol (Cm), an inhibitor of ribosomal peptidyl transferase activity, thereby inhibiting bacterial growth. The producer escapes autoinhibition by its own secondary metabolite through phosphorylation of Cm by chloramphenicol phosphotransferase (CPT). In addition to active site binding, CPT binds its product 3‐phosphoryl‐Cm, in an alternate product binding site. To address the...

Abstract The three‐dimensional structure of the Fab fragment of a monoclonal antibody (LNKB‐2) to human interleukin‐2 (IL‐2) complexed with a synthetic antigenic nonapeptide, Ac‐Lys‐Pro‐Leu‐Glu‐Glu‐Val‐Leu‐Asn‐Leu‐OMe, has been determined at 3.0 Å resolution. In the structure, four out of the six hypervariable loops of the Fab (complementarity determining regions [CDRs] L1, H1, H2, and H3) are involved in peptide association through...

Abstract Phage display is widely used for expression of combinatorial libraries, not least for protein engineering purposes. Precise selection at the single molecule level will provide an improved tool for generating proteins with complex and distinct properties from large molecular libraries. To establish such an improved selection system, we here report the detection of specific interactions between phage with displayed antibody...

Abstract The Profiles‐3D application, an inverse‐folding methodology appropriate for water‐soluble proteins, has been modified to allow the determination of structural properties of integral‐membrane proteins (IMPs) and for testing the validity of solved and model structures of IMPs. The modification, known as reverse‐environment prediction of integral membrane protein structure (REPIMPS), takes into account the fact that exposed...

Abstract The ferredoxin from the thermophilic archaeon Acidianus ambivalens is a small monomeric seven‐iron protein with a thermal midpoint (Tm) of 122°C (pH 7). To gain insight into the basis of its thermostability, we have characterized unfolding reactions induced chemically and thermally at various pHs. Thermal unfolding of this ferredoxin, in the presence of various guanidine hydrochloride (GuHCl) concentrations, yields a linear correlation...

Abstract Although the crystal structure of Vibrio harveyi luciferase has been elucidated, the binding sites for the flavin mononucleotide and fatty aldehyde substrates are still unknown. The determined location of the phosphate‐binding site close to Arg 107 on the α subunit of luciferase is supported here by point mutagenesis. This information, together with previous structure‐activity data for the length of the linker connecting ...

Abstract The goal of this study is to verify the concept of the funnel‐like intermolecular energy landscape in protein–protein interactions by use of a series of computational experiments. Our preliminary analysis revealed the existence of the funnel in many protein–protein interactions. However, because of the uncertainties in the modeling of these interactions and the ambiguity of the analysis procedures, the detection of the...

Abstract The binding of P1 variants of bovine pancreatic trypsin inhibitor (BPTI) to trypsin has been investigated by means of molecular dynamics simulations. The specific interaction formed between the amino acid at the primary binding (P1) position of the binding loop of BPTI and the specificity pocket of trypsin was estimated by use of the linear interaction energy (LIE) method. Calculations for 13 of the naturally occurring...

Abstract Protein‐tyrosine phosphatases catalyze the hydrolysis of phosphate monoesters via a two‐step mechanism involving a covalent phospho‐enzyme intermediate. Biochemical and site‐directed mutagenesis experiments show that the invariant Cys residue present in the PTPase signature motif (H/V)CX5R(S/T) (i.e., C215 in PTP1B) is absolutely required for activity. Mutation of the invariant Cys to Ser results in a catalytically inactive...

Abstract Transthyretin (TTR) subunits were labeled with a charge‐modifying tag to evaluate the possibility of subunit exchange between tetramers under physiological conditions. Starting with a mixture of two TTR homotetramers, one having all subunits tagged at the N termini and the other composed of untagged subunits, heterotetramer formation as a function of time and temperature was evaluated using ion exchange chromatography. The...

Abstract The platelet integrin αIIbβ3 is representative of a class of heterodimeric receptors that upon activation bind extracellular macromolecular ligands and form signaling clusters. This study examined how occupancy of αIIbβ3's fibrinogen binding site affected the receptor's solution structure and stability. Eptifibatide, an integrin antagonist developed to treat cardiovascular disease, served as a high‐affinity, monovalent...

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