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Journal Issue - Volume 15 Issue 1 (January 2006)

Abstract Symmetry, and in particular point group symmetry, is generally the rule for the global arrangement between subunits in homodimeric and other oligomeric proteins. The structures of fragments of tropomyosin and bovine fibrinogen are recently published examples, however, of asymmetric interactions between chemically identical chains. Their departures from strict twofold symmetry are based on simple and generalizable chemical...

Abstract Engineered antibodies and their fragments are invaluable tools for a vast range of biotechnological and pharmaceutical applications. However, they are facing increasing competition from a new generation of protein display scaffolds, specifically selected for binding virtually any target. Some of them have already entered clinical trials. Most of these nonimmunoglobulin proteins are involved in natural binding events and...

Abstract A docking‐and‐alignment protocol was devised in order to build amyloid protofilaments of Transthyretin (TTR), starting from partially disrupted TTR monomeric subunits and based on experimentally available information. The docking approach is driven by a combination of shape complementarity and energetic criteria, and uses constraints derived from experimental data obtained for the fibrillar state. The dimeric structures...

Abstract The role of disulfide bridges in the structure, stability, and folding pathways of proteins has been the subject of wide interest in the fields of protein design and engineering. However, the relative importance of entropic and enthalpic contributions for the stabilization of proteins provided by disulfides is not always clear. Here, we perform a detailed analysis of the role of disulfides in the conformational stability of...

Abstract Redox‐sensitive variants of the green fluorescent protein (roGFPs) had previously been developed that allow “real‐time” monitoring of the redox status of cellular compartments by fluorescence excitation ratiometry. However, the response time of these probes limits the study of certain rapid oxidative events, such as H2O2 bursts in cell signaling. The substitution of up to three positively charged amino acids adjacent to the introduced...

Abstract X‐ray crystal structures of human soluble epoxide hydrolase (sEH) complexed with four different dialkylurea inhibitors bearing pendant carboxylate “tails” of varying length have been determined at 2.3–3.0 Å resolution. Similarities among inhibitor binding modes reinforce the proposed roles of Y381 and/or Y465 as general acids that protonate the epoxide ring of the substrate in concert with nucleophilic attack of D333 at the...

Abstract The ability of proteins to regulate their own enzymatic activity can be facilitated by changes in structure or protein dynamics in response to external regulators. Because many proteins contain SH2 and SH3 domains, transmission of information between the domains is a potential method of allosteric regulation. To determine if ligand binding to one modular domain may alter structural dynamics in an adjacent domain, allowing...

Abstract The polyproline type II (PPII) helix is a prevalent conformation in both folded and unfolded proteins, and is known to play important roles in a wide variety of biological processes. Polyproline itself can also form a type I (PPI) helix, which has a disparate conformation. Here, we use derivatives of polyproline, (Pro)10, (Hyp)10, (Flp)10, and (flp)10, where Hyp is (2S,4R)‐4‐hydroxyproline, Flp is (2S,4R)‐4‐fluoroproline, and flp is...

Abstract Site‐2 proteases (S2Ps) form a large family of membrane‐embedded metalloproteases that participate in cellular signaling pathways through sequential cleavage of membrane‐tethered substrates. Using sequence similarity searches, we extend the S2P family to include remote homologs that help define a conserved structural core consisting of three predicted transmembrane helices with traditional metalloprotease functional motifs...

Abstract Hundreds of bacterial chemoreceptors from many species have periplasmic, ligand‐recognition domains of approximately the same size, but little or no sequence identity. The only structure determined is for the periplasmic domain of chemoreceptor Tar from Salmonella and Escherichia coli. Do sequence‐divergent but similarly sized chemoreceptor periplasmic domains have related structures? We addressed this issue for the...

Abstract Patterns of alternation of hydrophobic and polar residues are a profound aspect of amino acid sequences, but a feature not easily interpreted for soluble proteins. Here we report statistics of hydrophobicity patterns in proteins of known structure in a current protein database as compared with results from earlier, more limited structure sets. Previous studies indicated that long hydrophobic runs, common in membrane...

Abstract Cyclic AMP activates protein kinase A by binding to an inhibitory regulatory (R) subunit and releasing inhibition of the catalytic (C) subunit. Even though crystal structures of regulatory and catalytic subunits have been solved, the precise molecular mechanism by which cyclic AMP activates the kinase remains unknown. The dynamic properties of the cAMP binding domain in the absence of cAMP or C‐subunit are also unknown....

Abstract The identification of surface‐exposed components of the major outer membrane protein (MOMP) of Chlamydia is critical for modeling its three‐dimensional structure, as well as for understanding the role of MOMP in the pathogenesis of Chlamydia‐related diseases. MOMP contains four variable domains (VDs). In this study, VDII and VDIV of Chlamydia trachomatis serovar F were proven to be surface‐located by immuno‐dot blot assay using monoclonal...

Abstract The possible conformational changes of DNA polymerase IV (Dpo4) before and after the nucleotidyl‐transfer reaction are investigated at the atomic level by dynamics simulations to gain insight into the mechanism of low‐fidelity polymerases and identify slow and possibly critical steps. The absence of significant conformational changes in Dpo4 before chemistry when the incoming nucleotide is removed supports the notion that...

Abstract TATA‐binding protein (TBP)‐interacting protein from the hyperthermophilic archaeon Thermococcus kodakaraensis strain KOD1 (Tk‐TIP26) is a possible transcription regulatory protein in Thermococcales. Here, we report the crystal structure of Tk‐TIP26 determined at 2.3 Å resolution with multiple‐wavelength anomalous dispersion (MAD) method. The overall structure of Tk‐TIP26 consists of two domains. The N‐terminal domain forms an α/β structure, in...

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