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Journal Issue - Volume 12 Issue 9 (September 2003)

Abstract The success of structural genomics initiatives requires the development and application of tools for structure analysis, prediction, and annotation. In this paper we review recent developments in these areas; specifically structure alignment, the detection of remote homologs and analogs, homology modeling and the use of structures to predict function. We also discuss various rationales for structural genomics initiatives....

Abstract Malate synthase, an enzyme of the glyoxylate pathway, catalyzes the condensation and subsequent hydrolysis of acetyl‐coenzyme A (acetyl‐CoA) and glyoxylate to form malate and CoA. In the present study, we present the 1.95 Å–resolution crystal structure of Escherichia coli malate synthase isoform G in complex with magnesium, pyruvate, and acetyl‐CoA, and we compare it with previously determined structures of substrate and...

Abstract The correct delivery of noncytoplasmic proteins to locations both within and outside the cell depends on the appropriate targeting signals. Protein translocation across the bacterial plasma membrane and the eukaryal endoplasmic reticulum membrane relies on cleavable N‐terminal signal peptides. Although the signal peptides of secreted proteins in Bacteria and Eukarya have been extensively studied at the sequence, structure,...

Abstract Pi4 is a short toxin found at very low abundance in the venom of Pandinus imperator scorpions. It is a potent blocker of K+ channels. Like the other members of the α‐KTX6 subfamily to which it belongs, it is cross‐linked by four disulfide bonds. The synthetic analog (sPi4) and the natural toxin (nPi4) have been obtained by solid‐phase synthesis or from scorpion venom, respectively. Analysis of two‐dimensional 1H NMR spectra of nPi4 and...

Abstract Bacterial muconate lactonizing enzymes (MLEs) catalyze the conversion of cis,cis‐muconate as a part of the β‐ketoadipate pathway, and some MLEs are also able to dehalogenate chlorinated muconates (Cl‐MLEs). The basis for the Cl‐MLEs dehalogenating activity is still unclear. To further elucidate the differences between MLEs and Cl‐MLEs, we have solved the structure of Pseudomonas P51 Cl‐MLE at 1.95 Å resolution. Comparison of...

Abstract Estimating the number of molecules in the crystallographic asymmetric unit is one of the first steps in a macromolecular structure determination. Based on a survey of 15,641 crystallographic Protein Data Bank (PDB) entries the distribution of VM, the crystal volume per unit of protein molecular weight, known as Matthews coefficient, has been reanalyzed. The range of values and frequencies has changed in the 30 years since Matthews...

Abstract The PAAD/DAPIN/pyrin domain is the fourth member of the death domain superfamily, but unlike other members of this family, it is involved not only in apoptosis but also in innate immunity and several other processes. We have identified 40 PAAD domain‐containing proteins by extensively searching the genomes of higher eukaryotes and viruses. Phylogenetic analyses suggest that there are five categories of PAAD domains that...

Abstract We have investigated free energy landscape [MM/PBSA + normal modes entropy] of permutations in the G peptide (41–56) from the protein G B1 domain by studying six isomers corresponding to moving the hydrophobic cluster along the β‐strands (toward the turn: T1, AGEWTYDDKTFTVTET; T2, GEDTWDYATFTVTKTE; T3, GEDDWTYATFTVTKTE; toward the end: E1, WTYDDAGETKTFTVT; E2, WEYTGDDATKTETFTV; E3, WTYEGDDATKTETFTV). The free energy terms...

Abstract The ionization properties of the active‐site residues in enzymes are of considerable interest in the study of the catalytic mechanisms of enzymes. Knowledge of these ionization constants (pKa values) often allows the researcher to identify the proton donor and the catalytic nucleophile in the reaction mechanism of the enzyme. Estimates of protein residue pKa values can be obtained by applying pKa calculation algorithms to...

Abstract 3‐Nitro‐4‐hydroxybenzoate (3N4H) is a probe of the structure and dynamics of the metal‐centered His B10 assembly sites of the insulin hexamer. Each His B10 site consists of a ∼12 Å‐long cavity situated on the threefold symmetry axis. These sites play an important role in the storage and release of insulin in vivo. The allosteric behavior of the insulin hexamer is modulated by ligand binding to the His B10 zinc sites and to...

Abstract A number of regulatory binding sites of glycogen phosphorylase (GP), such as the catalytic, the inhibitor, and the new allosteric sites are currently under investigation as targets for inhibition of hepatic glycogenolysis under high glucose concentrations; in some cases specific inhibitors are under evaluation in human clinical trials for therapeutic intervention in type 2 diabetes. In an attempt to investigate whether the...

Abstract PABC is a phylogenetically conserved peptide‐binding domain primarily found within the C terminus of poly(A)‐binding proteins (PABPs). This domain recruits a series of translation factors including poly(A)‐interacting proteins (Paip1 and Paip2) and release factor 3 (RF3/GSPT) to the initiation complex on mRNA. Here, we determine the solution structure of the Trypanosoma cruzi PABC domain (TcPABC), a representative of the vegetal class...

Abstract Phospholipases C (PLCs) reversibly associate with membranes to hydrolyze phosphatidylinositol‐4, 5‐bisphosphate (PI[4,5]P2) and comprise four main classes: β, γ, δ, and ε. Most eukaryotic PLCs contain a single, N‐terminal pleckstrin homology (PH) domain, which is thought to play an important role in membrane targeting. The structure of a single PLC PH domain, that from PLCδ1, has been determined; this PH domain binds PI(4,5)P2 with...

Abstract Mycothiol is the predominant low‐molecular weight thiol produced by actinomycetes, including Mycobacterium tuberculosis. The last reaction in the biosynthetic pathway for mycothiol is catalyzed by mycothiol synthase (MshD), which acetylates the cysteinyl amine of cysteine–glucosamine–inositol (Cys–GlcN–Ins). The crystal structure of MshD was determined in the presence of coenzyme A and acetyl–CoA. MshD consists of two tandem‐repeated...

Abstract Receptor signaling in the growth hormone (GH)–growth hormone receptor (GHR) system is controlled through a sequential two‐step hormone‐induced dimerization of two copies of the extracellular domain (ECD) of the receptor. The regulatory step of this process is the binding of the second ECD (ECD2) to the stable preassociated 1 : 1 GH/ECD1 complex on the cell surface. To determine the energetics that governs this step, the...

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