Main-chain Bond Lengths and Bond Angles in Protein Structures

Laskowski, Roman A.; Moss, David S.; Thornton, Janet M.

doi:10.1006/jmbi.1993.1351

Cited by 1,151 publications

(899 citation statements)

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“…(RR) 5 peptides were identified in the final electron density maps of CAR2.V1. The program PROCHECK [48] was used to validate the final structures, and PyMOL was used to generate figures [49].…”

Section: Crystallization and Structure Determinationmentioning

confidence: 99%

Computationally Designed Armadillo Repeat Proteins for Modular Peptide Recognition

Reichen

Hansen

Forzani

et al. 2016

Journal of Molecular Biology

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Armadillo repeat proteins (ArmRP) recognize their target peptide in extended conformation and bind, in a first approximation, two residues per repeat. They may thus form the basis for building a modular system, in which each repeat is complementary to a piece of the target peptide. Accordingly, preselected repeats could be assembled into specific binding proteins on demand and thereby avoid the traditional generation of every new binding molecule by an independent selection from a library.Stacked armadillo repeats, each consisting of 42 amino acids arranged in three α-helices, build an elongated superhelical structure. Here, we analyzed curvature variations in natural ArmRPs, and identified a repeat pair from yeast importin-α as having the optimal curvature geometry to be complementary to a peptide over its whole length. We employed a symmetric in silico design to obtain a uniform sequence for a stackable repeat while maintaining the desired curvature geometry.Computationally designed armadillo repeat proteins (dArmRPs) had to be stabilized by mutations to remove regions of higher flexibility, which were identified by molecular dynamics (MD) simulations in explicit solvent. Using an N-capping repeat from the consensus-design approach, two different crystal structures of dArmRP were determined. Although the experimental structures of dArmRP deviated from the designed curvature, the insertion of the most conserved binding pockets of natural ArmRPs onto the surface of dArmRPs resulted in binders against the expected peptide with low nanomolar affinities, similar to the binders from the consensus-design series.

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Section: Crystallization and Structure Determinationmentioning

confidence: 99%

Computationally Designed Armadillo Repeat Proteins for Modular Peptide Recognition

Reichen

Hansen

Forzani

et al. 2016

Journal of Molecular Biology

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“…42 Simulated annealing was performed in PHENIX. 43 The structure was validated using the programs PRO-CHECK (version 3.5.4), 44 ERRAT, 45 and VERI-FY_3D. 46 Although addition of NAD to the crystallization solution improved the size and quality of the crystals, no clear electron density was observed for NAD.…”

Section: Esi Mass Spectrometrymentioning

confidence: 99%

Structure of the dimerization domain of DiGeorge Critical Region 8

et al. 2010

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Maturation of microRNAs (miRNAs,~22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 Å resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

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“…dcSAH was successfully positioned in both chains present in the asymmetric unit; however, no density was seen for the putrescine molecule, and the putrescine binding site was occupied by water molecules. The final refinement statistics are given in Table II, where the Ramachandran plot statistics were calculated using PROCHECK 29 and showed the partially solventexposed Glu208 in each chain to be in the disallowed region.…”

Section: Structure Determination and Refinementmentioning

confidence: 99%

Binding and inhibition of human spermidine synthase by decarboxylated S‐adenosylhomocysteine

Šečkutė¹,

McCloskey²,

Thomas³

et al. 2011

Protein Science

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Aminopropyltransferases are essential enzymes that form polyamines in eukaryotic and most prokaryotic cells. Spermidine synthase (SpdS) is one of the most well-studied enzymes in this biosynthetic pathway. The enzyme uses decarboxylated S-adenosylmethionine and a short-chain polyamine (putrescine) to make a medium-chain polyamine (spermidine) and 5 0 -deoxy-5 0 -methylthioadenosine as a byproduct. Here, we report a new spermidine synthase inhibitor, decarboxylated S-adenosylhomocysteine (dcSAH). The inhibitor was synthesized, and dosedependent inhibition of human, Thermatoga maritima, and Plasmodium falciparum spermidine synthases, as well as functionally homologous human spermine synthase, was determined. The human SpdS/dcSAH complex structure was determined by X-ray crystallography at 2.0 Å resolution and showed consistent active site positioning and coordination with previously known structures. Isothermal calorimetry binding assays confirmed inhibitor binding to human SpdS with K d of 1.1 6 0.3 lM in the absence of putrescine and 3.2 6 0.1 lM in the presence of putrescine. These results indicate a potential for further inhibitor development based on the dcSAH scaffold.

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Main-chain Bond Lengths and Bond Angles in Protein Structures

Cited by 1,151 publications

References 0 publications

Computationally Designed Armadillo Repeat Proteins for Modular Peptide Recognition

Computationally Designed Armadillo Repeat Proteins for Modular Peptide Recognition

Structure of the dimerization domain of DiGeorge Critical Region 8

Binding and inhibition of human spermidine synthase by decarboxylated S‐adenosylhomocysteine

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