On residues in the disallowed region of the Ramachandran map

Pal, Debnath; Chakrabarti, Pinak

doi:10.1002/bip.10051

Cited by 77 publications

(72 citation statements)

References 25 publications

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“…7. 94 In the aqueous region of the simulation box, the φ and ψ angles of NAFA, NAYA, and NATA are grouped into three areas: the large region with negative ψ angles represents α-helical type conformations, the region in the top left corner-β-sheet and extended structures, and the small region in-between the C 7eq conformer characteristic of dipeptides. 95 As the dipeptides move from solution to interface, the probabilities in the α and β regions decrease, while that of C 7eq increases.…”

Section: Backbone Conformationsmentioning

confidence: 99%

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Lee

Kuczera

Middaugh

et al. 2016

The Journal of Chemical Physics

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The time-resolved parallel artificial membrane permeability assay with fluorescence detection and comprehensive computer simulations are used to study the passive permeation of three aromatic dipeptides—N-acetyl-phenylalanineamide (NAFA), N-acetyltyrosineamide (NAYA), and N-acetyl-tryptophanamide (NATA) through a 1,2-dioleoyl-sn-glycero-3-phospocholine (DOPC) lipid bilayer. Measured permeation times and permeability coefficients show fastest translocation for NAFA, slowest for NAYA, and intermediate for NATA under physiological temperature and pH. Computationally, we perform umbrella sampling simulations to model the structure, dynamics, and interactions of the peptides as a function of z, the distance from lipid bilayer. The calculated profiles of the potential of mean force show two strong effects—preferential binding of each of the three peptides to the lipid interface and large free energy barriers in the membrane center. We use several approaches to calculate the position-dependent translational diffusion coefficients D(z), including one based on numerical solution the Smoluchowski equation. Surprisingly, computed D(z) values change very little with reaction coordinate and are also quite similar for the three peptides studied. In contrast, calculated values of sidechain rotational correlation times τrot(z) show extremely large changes with peptide membrane insertion—values become 100 times larger in the headgroup region and 10 times larger at interface and in membrane center, relative to solution. The peptides’ conformational freedom becomes systematically more restricted as they enter the membrane, sampling α and β and C7eq basins in solution, α and C7eq at the interface, and C7eq only in the center. Residual waters of solvation remain around the peptides even in the membrane center. Overall, our study provides an improved microscopic understanding of passive peptide permeation through membranes, especially on the sensitivity of rotational diffusion to position relative to the bilayer.

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Section: Backbone Conformationsmentioning

confidence: 99%

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Lee

Kuczera

Middaugh

et al. 2016

The Journal of Chemical Physics

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“…Gunasekaran et al (42) found such conformations in the second position (iϩ1) of perfect type IIЈ ␤-turns. In a follow-up on this work, Pal and Chakrabarti (43) reported that such residues (in their nomenclature, "region II" residues) are "common in the first position of 3 10 -helices, which in the majority of cases lead into ␣-helices." As type IIЈ ␤-turns are essentially short 3 10 -helices, the results of Gunasekaran et al and Pal and Chakrabarti are perfectly consistent.…”

Section: Discussionmentioning

confidence: 92%

Pseudomonas aeruginosa LD-Carboxypeptidase, a Serine Peptidase with a Ser-His-Glu Triad and a Nucleophilic Elbow*

Korza¹,

Bochtler²

2005

Journal of Biological Chemistry

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LD-Carboxypeptidases (EC 3.4.17.13) are named for their ability to cleave amide bonds between L-and D-amino acids, which occur naturally in bacterial peptidoglycan. They are specific for the link between meso-diaminopimelic acid and D-alanine and therefore degrade GlcNAc-MurNAc tetrapeptides to the corresponding tripeptides. As only the tripeptides can be reused as peptidoglycan building blocks, LD-carboxypeptidases are thought to play a role in peptidoglycan recycling. Despite the pharmaceutical interest in peptidoglycan biosynthesis, the fold and catalytic type of LD-carboxypeptidases are unknown. Here, we show that a previously uncharacterized open reading frame in Pseudomonas aeruginosa has LD-carboxypeptidase activity and present the crystal structure of this enzyme. The structure shows that the enzyme consists of an N-terminal ␤-sheet and a C-terminal ␤-barrel domain. At the interface of the two domains, Ser 115 adopts a highly strained conformation in the context of a strand-turn-helix motif that is similar to the "nucleophilic elbow" in ␣␤-hydrolases. Ser 115 is hydrogen-bonded to a histidine residue, which is oriented by a glutamate residue. All three residues, which occur in the order Ser-Glu-His in the amino acid sequence, are strictly conserved in naturally occurring LD-carboxypeptidases and cannot be mutated to alanines without loss of activity. We conclude that LD-carboxypeptidases are serine peptidases with Ser-His-Glu catalytic triads.LD-Carboxypeptidases have been named for their unusual ability to cleave amide bonds that link an L-amino acid to a C-terminal D-amino acid. The physiological substrates are tetrapeptide peptidoglycan fragments that contain an L-configured residue (L-lysine or a suitably oriented meso-diaminopimelic acid residue) as the penultimate residue and D-alanine as the ultimate residue. LD-Carboxypeptidase substrates are produced when cell walls are degraded. It is thought that these fragments cannot be reincorporated into murein in the absence of LDcarboxypeptidase activity. In the presence of LD-carboxypeptidase activity, the tetrapeptides are truncated to tripeptides, which can then be reconverted into peptidoglycan building blocks by the attachment of preformed D-Ala-D-Ala dipeptides.

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“…This cluster falls into one of the six clusters identified in the earlier analyses. 51,52 The backbone conformation of the residues in this cluster corresponds to the i+1 position of a type II' β-turn. [53][54][55] Incidentally, the histidinecontaining phosphocarrier protein also has a disallowed residue (Ala16) falling in this cluster.…”

Section: Are Ramachandran Disallowed Conformations Frequent In Class mentioning

confidence: 99%

How Different are Structurally Flexible and Rigid Binding Sites? Sequence and Structural Features Discriminating Proteins that Do and Do not Undergo Conformational Change upon Ligand Binding

Gunasekaran¹,

Nussinov²

2007

Journal of Molecular Biology

128

110

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On residues in the disallowed region of the Ramachandran map

Cited by 77 publications

References 25 publications

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Pseudomonas aeruginosa LD-Carboxypeptidase, a Serine Peptidase with a Ser-His-Glu Triad and a Nucleophilic Elbow*

How Different are Structurally Flexible and Rigid Binding Sites? Sequence and Structural Features Discriminating Proteins that Do and Do not Undergo Conformational Change upon Ligand Binding

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