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Journal Issue - Volume 16 Issue 2 (February 2007)

Abstract We describe the development of a method for assembling structures of multidomain proteins from structures of isolated domains. The method consists of an initial low‐resolution search in which the conformational space of the domain linker is explored using the Rosetta de novo structure prediction method, followed by a high‐resolution search in which all atoms are treated explicitly and backbone and side chain degrees of...

Abstract Rcd‐1, a protein highly conserved across eukaryotes, was initially identified as a factor essential for nitrogen starvation‐invoked differentiation in fission yeast, and its Saccharomyces cerevisiae homolog, CAF40, has been identified as part of the CCR4–NOT transcription complex, where it interacts with the NOT1 protein. Mammalian homologs are involved in various cellular differentiation processes including retinoic acid‐induced...

Abstract Myosins play essential roles in migration, cytokinesis, endocytosis, and adhesion. They are composed of a large N‐terminal motor domain with ATPase and actin binding sites and C‐terminal neck and tail regions, whose functional roles and structural context in the protein are less well characterized. The tail regions of myosins I, IV, VII, XII, and XV each contain a putative SH3 domain that may be involved in protein–protein...

Abstract We have recently shown that two flexible loops of Streptomyces phospholipase D (PLD) affect the catalytic reaction of the enzyme by a comparative study of chimeric PLDs. Gly188 and Asp191 of PLD from Streptomyces septatus TH‐2 (TH‐2PLD) were identified as the key amino acid residues involved in the recognition of phospholipids. In the present study, we further investigated the relationship between a C‐terminal loop of TH‐2PLD and PLD...

Abstract Collagen is the most abundant protein in animals. Every third residue in a collagen strand is a glycine with φ, ψ = −70°, 175°. A recent computational study suggested that replacing these glycine residues with d‐alanine or d‐serine would stabilize the collagen triple helix. This hypothesis is of substantial importance, as the glycine residues in collagen constitute nearly 10% of the amino acid residues in humans. To test this...

Abstract Structural genomics projects are determining the three‐dimensional structure of proteins without full characterization of their function. A critical part of the annotation process involves appropriate knowledge representation and prediction of functionally important residue environments. We have developed a method to extract features from sequence, sequence alignments, three‐dimensional structure, and structural environment...

Abstract A thermodynamic analysis of a cold‐adapted protein, type III anti‐freeze protein (AFP), was carried out. The results indicate that the folding equilibrium of type III AFP is a reversible, unimolecular, two‐state process with no populated intermediates. Compared to most mesophilic proteins whose folding is two‐state, the psychrophilic type III AFP has a much lower thermodynamic stability at 25°C, ∼3 kcal/mol, and presents a...

  • Redesigning protein pK a values

  • Barbara Mary Tynan‐Connolly, Jens Erik Nielsen
  • Published in Wiley Interscience on Jan 01, 2009
  • DOI: 10.1110/ps.062538707 (p 239-249)

Abstract The ability to re‐engineer enzymatic pH‐activity profiles is of importance for industrial applications of enzymes. We theoretically explore the feasibility of re‐engineering enzymatic pH‐activity profiles by changing active site pKa values using point mutations. We calculate the maximum achievable ΔpKa values for 141 target titratable groups in seven enzymes by introducing conservative net‐charge altering point mutations. We examine...

Abstract Synechocystis hemoglobin contains an unprecedented covalent bond between a nonaxial histidine side chain (H117) and the heme 2‐vinyl. This bond has been previously shown to stabilize the ferric protein against denaturation, and also to affect the kinetics of cyanide association. However, it is unclear why Synechocystis hemoglobin would require the additional degree of stabilization accompanying the His117–heme 2‐vinyl bond because it...

Abstract Two distinct ways of organizing fatty acid biosynthesis exist: the multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and lower eukaryotes with activities residing on one or two polypeptides; and the dissociated type II FAS of prokaryotes, plastids, and mitochondria with individual activities encoded by discrete genes. The β‐ketoacyl [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted...

Abstract Local structures in denatured proteins may be important in guiding a polypeptide chain during the folding and misfolding processes. Existence of local structures in chemically denatured proteins is a highly controversial issue. NMR parameters [coupling constants 3J(Hα,HN) and chemical shifts] of chemically denatured proteins in general deviate little from their values in small peptides. These peptides were presumed to be...

Abstract Fertilin is a transmembrane protein heterodimer formed by the two subunits fertilin α and fertilin β that plays an important role in sperm–egg fusion. Fertilin α and β are members of the ADAM family, and contain each one transmembrane α‐helix, and are termed ADAM 1 and ADAM 2, respectively. ADAM 1 is the subunit that contains a putative fusion peptide, and we have explored the possibility that the transmembrane α‐helical...

Abstract Mixtures of organic osmolytes occur in cells of many organisms, raising the question of whether their actions on protein stability are independent or synergistic. To investigate this question it is desirable to develop a system that permits evaluation of the effect of one osmolyte on the efficacy of another to either force‐fold or denature a protein. A means of evaluating the efficacy of an osmolyte is provided by its...

Abstract MHC class I molecules load antigenic peptides in the endoplasmic reticulum and present them at the cell surface. Efficiency of peptide loading depends on the class I allele and can involve interaction with tapasin and other proteins of the loading complex. Allele HLA‐B*4402 (Asp at position 116) depends on tapasin for efficient peptide loading, whereas HLA‐B*4405 (identical to B*4402 except for Tyr116) can efficiently load...

Abstract Various nonglycosylated analogs were designed in order to explore the role of glycosylation in formaecin I, an antibacterial glycopeptide of insect origin. The functional behavior of a designed nonglycosylated analog (P7,endo P8a,ΔT11)formaecin I was found to be similar to that of native glycosylated peptide. Both the peptides showed similar antibacterial activities against Escherichia coli and Salmonella strains. The designed...

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