Classification of Domain Movements in Proteins Using Dynamic Contact Graphs

Taylor, Daniel; Cawley, Gavin C.; Hayward, Steven

doi:10.1371/journal.pone.0081224

Cited by 19 publications

(20 citation statements)

References 20 publications

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“…Relative domain movements were analysed using the DynDom website (Hayward & Berendsen, 1998;Hayward & Lee, 2002). The hinge and shear classification of the domain movements was determined using the dynamic contact graphs (DCG) method described by Taylor et al (2013Taylor et al ( , 2014. This The electron-density map for the DPM cofactor.…”

Section: Determination and Classification Of Domain Movementsmentioning

confidence: 99%

Structural studies of domain movement in active-site mutants of porphobilinogen deaminase fromBacillus megaterium

et al. 2017

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The enzyme porphobilinogen deaminase (PBGD) is one of the key enzymes in tetrapyrrole biosynthesis. It catalyses the formation of a linear tetrapyrrole from four molecules of the substrate porphobilinogen (PBG). It has a dipyrromethane cofactor (DPM) in the active site which is covalently linked to a conserved cysteine residue through a thioether bridge. The substrate molecules are linked to the cofactor in a stepwise head-to-tail manner during the reaction, which is catalysed by a conserved aspartate residue: Asp82 in the B. megaterium enzyme. Three mutations have been made affecting Asp82 (D82A, D82E and D82N) and their crystal structures have been determined at resolutions of 2.7, 1.8 and 1.9 Å, respectively. These structures reveal that whilst the D82E mutant possesses the DPM cofactor, in the D82N and D82A mutants the cofactor is likely to be missing, incompletely assembled or disordered. Comparison of the mutant PBGD structures with that of the wild-type enzyme shows that there are significant domain movements and suggests that the enzyme adopts `open' and `closed' conformations, potentially in response to substrate binding.

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Section: Determination and Classification Of Domain Movementsmentioning

confidence: 99%

Structural studies of domain movement in active-site mutants of porphobilinogen deaminase fromBacillus megaterium

et al. 2017

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“…In the course of time, our work progressively demonstrated that this phenomenon could be observed in a wider range of proteins with little or no significant evolutionary relation to the previous ones [6–8]. Moreover, similarly to some protein folding methodological studies that “sees” the polypeptide chain as an assembly of particular sub-sets of smaller fragments orderable in a hierarchical process to yield the final protein architecture, such as: building blocks (microdomains), hydrophobic folding units (subdomains), protein domain, protein fold (multidomains) and quaternary structure [9–14], we have also located inside a number of protein primary structures, shorter amino acid sequences active against pathogenic microorganisms, potent opioids and hypotensive agents [6,7].…”

Section: Introductionmentioning

confidence: 99%

Intragenic antimicrobial peptides (IAPs) from human proteins with potent antimicrobial and anti-inflammatory activity

Brand¹,

Ramada²,

Manickchand³

et al. 2019

PLoS ONE

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Following the treads of our previous works on the unveiling of bioactive peptides encrypted in plant proteins from diverse species, the present manuscript reports the occurrence of four proof-of-concept intragenic antimicrobial peptides in human proteins, named Hs IAPs. These IAPs were prospected using the software Kamal, synthesized by solid phase chemistry, and had their interactions with model phospholipid vesicles investigated by differential scanning calorimetry and circular dichroism. Their antimicrobial activity against bacteria, yeasts and filamentous fungi was determined, along with their cytotoxicity towards erythrocytes. Our data demonstrates that Hs IAPs are capable to bind model membranes while attaining α-helical structure, and to inhibit the growth of microorganisms at concentrations as low as 1μM. Hs02, a novel sixteen residue long internal peptide ( ) derived from the unconventional myosin 1h protein, was further investigated in its capacity to inhibit lipopolysaccharide-induced release of TNF-α in murine macrophages. Hs02 presented potent anti-inflammatory activity, inhibiting the release of TNF-α in LPS-primed cells at the lowest assayed concentration, 0.1 μM. A three-dimensional solution structure of Hs02 bound to DPC micelles was determined by Nuclear Magnetic Resonance. Our work exemplifies how the human genome can be mined for molecules with biotechnological potential in human health and demonstrates that IAPs are actual alternatives to antimicrobial peptides as pharmaceutical agents or in their many other putative applications.

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“…At the all-atom level, a cut-off distance of 4 Å proved to be the most common optimal value, a distance that is often used as an atomic contact distance between non-bonded atoms, e.g. as in the contact of two domains in a protein (Taylor, et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Morphing and docking visualisation of biomolecular structures using Multi-Dimensional Scaling

Veevers

Hayward

2018

Journal of Molecular Graphics and Modelling

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Protein structures are often solved at atomic resolution in two states defining a functional movement but intervening conformations are usually unknown. Morphing methods generate intervening conformations between two known structures. When viewed as an animation using molecular graphics, a smooth, direct morph enables the eye to track changes in structure that might be otherwise missed. We present a morphing method that aims to linearly interpolate interatomic distances and which uses SMACOF (Scaling by MAjorisation of COmplicated Function) and multigrid techniques with a cut-off distance based weighting that optimizes the MolProbity score of intervening structures. The all-atom morphs are smooth, move directly between the two structures, and are shown, in general, to pass closer to a set of known intermediates than those generated using other methods. The techniques are also used for docking by putting the unbound structures in a "near-approach pose" and then morphing to the bound complex. The resulting GPU-accelerated tools are available on a webserver, Morphit_Pro, at http://morphit-pro.cmp.uea.ac.uk/ and more than 5000 domains movements available at the DynDom website can now be viewed as morphs http://morphit-pro.cmp.uea.ac.uk/dyndom/.

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Classification of Domain Movements in Proteins Using Dynamic Contact Graphs

Cited by 19 publications

References 20 publications

Structural studies of domain movement in active-site mutants of porphobilinogen deaminase fromBacillus megaterium

Structural studies of domain movement in active-site mutants of porphobilinogen deaminase fromBacillus megaterium

Intragenic antimicrobial peptides (IAPs) from human proteins with potent antimicrobial and anti-inflammatory activity

Morphing and docking visualisation of biomolecular structures using Multi-Dimensional Scaling

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