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Journal Issue - Volume 8 Issue 9 (1999)

Abstract The 2.1 Å resolution crystal structure of flavin reductase P with the inhibitor nicotinamide adenine dinucleotide (NAD) bound in the active site has been determined. NAD adopts a novel, folded conformation in which the nicotinamide and adenine rings stack in parallel with an inter‐ring distance of 3.6 Å. The pyrophosphate binds next to the flavin cofactor isoalloxazine, while the stacked nicotinamide/adenine moiety faces...

Abstract We describe a novel N‐terminal α‐helix local motif that involves three hydrophobic residues and a Pro residue (Pro‐box motif). Database analysis shows that when Pro is the N‐cap of an α‐helix the distribution of amino acids in adjacent positions changes dramatically with respect to the average distribution in an α‐helix, but not when Pro is at position N1. N‐cap Pro residues are usually associated to Ile and Leu, at position N', Val at...

Abstract S100B(ββ) is a dimeric Ca2+‐binding protein that interacts with p53, inhibits its phosphorylation by protein kinase C (PKC) and promotes disassembly of the p53 tetramer. Likewise, a 22 residue peptide derived from the C‐terminal regulatory domain of p53 has been shown to interact with S100B(ββ) in a Ca2+‐dependent manner and inhibits its phosphorylation by PKC. Hence, structural studies of Ca2+‐loaded S100B(ββ) bound to the p53 peptide...

Abstract We describe a new computational technique to predict conformationally switching elements in proteins from their amino acid sequences. The method, called ASP (Ambivalent Structure Predictor), analyzes results from a secondary structure prediction algorithm to identify regions of conformational ambivalence. ASP identifies ambivalent regions in 16 test protein sequences for which function involves substantial backbone...

Abstract The pokeweed antiviral protein (PAP) belongs to a family of ribosome‐inactivating proteins (RIP), which depurinate ribosomal RNA through their site‐specific N‐glycosidase activity. We report low temperature, three‐dimensional structures of PAP co‐crystallized with adenyl‐guanosine (ApG) and adenyl‐cytosine‐cytosine (ApCpC). Crystal structures of 2.0–2.1 Å resolution revealed that both ApG or ApCpC nucleotides are cleaved by...

Abstract The tumor suppressor function of the wild‐type p53 protein is transdominantly inhibited by tumor‐derived mutant p53 proteins. Such transdominant inhibition limits the prospects for gene therapy approaches that aim to introduce wild‐type p53 into cancer cells. The molecular mechanism for transdominant inhibition involves sequestration of wild‐type p53 subunits into inactive wild‐type/mutant hetero‐tetramers. Thus, p53...

Abstract We have recently constructed hyperactive human deoxyribonuclease I (DNase I) variants that digest double‐stranded DNA more efficiently under physiological saline conditions by introducing positively charged amino acids at eight positions that can interact favorably with the negatively charged DNA phosphates. In this study, we present data from supercoiled DNA nicking, linear DNA digestion, and hyperchromicity assays that...

Abstract The moderate thermophilic eubacterium Alicyclobacillus (formerly Bacillus) acidocaldarius expresses a thermostable carboxylesterase (esterase 2) belonging to the hormone‐sensitive lipase (HSL)‐like group of the esterase/lipase family. Based on secondary structures predictions and a secondary structure‐driven multiple sequence alignment with remote homologous protein of known three‐dimensional (3D) structure, we previously hypothesized...

Abstract Circular dichroism and NMR spectroscopy have been used to determine the structure of the low‐density lipoprotein (LDL) receptor‐binding peptide, comprising residues 130–152, of the human apolipoprotein E. This peptide has little persistent three‐dimensional structure in solution, but when bound to micelles of dodecylphosphocholine (DPC) it adopts a predominantly α‐helical structure. The three‐dimensional structure of the...

Abstract The sequences of several members of the myosin family of molecular motors are evaluated using ASP (Ambivalent Structure Predictor), a new computational method. ASP predicts structurally ambivalent sequence elements by analyzing the output from a secondary structure prediction algorithm. These ambivalent sequence elements form secondary structures that are hypothesized to function as switches by undergoing conformational...

Abstract Despite decades of intense study, the complementarity of β‐lactams for β‐lactamases and penicillin binding proteins is poorly understood. For most of these enzymes, β‐lactam binding involves rapid formation of a covalent intermediate. This makes measuring the equilibrium between bound and free β‐lactam difficult, effectively precluding measurement of the interaction energy between the ligand and the enzyme. Here, we explore...

Abstract Recent studies of the refolding of reduced bovine pancreatic trypsin inhibitor (BPTI) have shown that a previously unidentified intermediate with a single disulfide is formed much more rapidly than any other one‐disulfide species. This intermediate contains a disulfide that is present in the native protein (between Cys14 and 38), but it is thermodynamically less stable than the other two intermediates with single native...

Abstract It is difficult to increase protein stability by adding hydrogen bonds or burying nonpolar surface. The results described here show that reversing the charge on a side chain on the surface of a protein is a useful way of increasing stability. Ribonuclease T1 is an acidic protein with a pI ≈︁ 3.5 and a net charge of ≈︁ –6 at pH 7. The side chain of Asp49 is hyperexposed, not hydrogen bonded, and 8 Å from the nearest charged...

  • Role of the prosequence of guanylin

  • Axel Schulz, Ute C. Marx, Yuji Hidaka, Yasutsugu Shimonishi, Paul Rösch, Wolf‐Georg Forssmann, Knut Adermann
  • Published in Wiley Interscience on Dec 31, 2008
  • DOI: 10.1110/ps.8.9.1850 (p 1850-1859)

Abstract Guanylin is a guanylyl cyclase (GC)‐activating peptide that is mainly secreted as the corresponding prohormone of 94 amino acid residues. In this study, we show that the originally isolated 15‐residue guanylin, representing the COOH‐terminal part of the prohormone, is released from the prohormone by cleavage of an Asp‐Pro amide bond under conditions applied during the isolation procedures. Thus, the 15‐residue guanylin is...

Abstract This work experimentally confirms the pathway of activation of Ha‐ras‐p21, which was calculated by the method of Targeted Molecular Dynamics (TMD) (Díaz JF, Wroblowski B, Schlitter J, Engelborghs Y, 1997a, Proteins Struct Funct Genet 28:434–451). The process can be studied experimentally by analyzing the binding of BeF3− to the GDP complex of the active fluorescent mutant Y32W (Díaz JF, Sillen A, Engelborghs Y, 1997b, J Biol Chem 227:23138–23143)....

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