Missing strings of residues in protein crystal structures

Djinović-Carugo, Kristina; Carugo, Oliviero

doi:10.1080/21690707.2015.1095697

Cited by 48 publications

(34 citation statements)

References 18 publications

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“…Comparison of these metrics revealed some interesting cases and some of these results are worth to be underlined. Loop 5 had the highest B-factor (where some atoms are missing 43 ) and RMSF values. However, low N eq values indicate that a highly rigid zone forms the core of the loop.…”

Section: Discussionmentioning

confidence: 99%

In silico analysis of Glanzmann variants of Calf-1 domain of αIIbβ3 integrin revealed dynamic allosteric effect

Goguet

Narwani

Petermann

et al. 2017

Sci Rep

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Integrin αIIbβ3 mediates platelet aggregation and thrombus formation. In a rare hereditary bleeding disorder, Glanzmann thrombasthenia (GT), αIIbβ3 expression / function are impaired. The impact of deleterious missense mutations on the complex structure remains unclear. Long independent molecular dynamics (MD) simulations were performed for 7 GT variants and reference structure of the Calf-1 domain of αIIb. Simulations were analysed using a structural alphabet to describe local protein conformations. Common and flexible regions as well as deformable zones were observed in all the structures. The most flexible region of Calf-1 (with highest B-factor) is rather a rigid region encompassed into two deformable zones. Each mutated structure barely showed any modifications at the mutation sites while distant conformational changes were observed. These unexpected results question the relationship between molecular dynamics and allostery; and the role of these long-range effects in the impaired αIIbβ3 expression. This method is aimed at studying all αIIbβ3 sub-domains and impact of missense mutations at local and global structural level.

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Section: Discussionmentioning

confidence: 99%

In silico analysis of Glanzmann variants of Calf-1 domain of αIIbβ3 integrin revealed dynamic allosteric effect

Goguet

Narwani

Petermann

et al. 2017

Sci Rep

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“…Disorder regions are mainly defined as series of missing residues in X-ray structures taken from the PDB, they are highly frequent (more than 80% of the X-ray structures with a resolution worse than 1.75 Å have missing residues) (Djinovic- Carugo and Carugo 2015).…”

Section: In Context Of Protein Function This Diversity Leads To Coopmentioning

confidence: 99%

Investigation of the impact of PTMs on the protein backbone conformation

et al. 2019

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Post-Translational Modifications (PTMs) are known to play a critical role in the regulation of the protein functions. Their impact on protein structures, and their link to disorder regions have already been spotted on the past decade. Nonetheless, the high diversity of PTMs types, and the multiple schemes of protein modifications (multiple PTMs, of different types, at different time, etc) make difficult the direct confrontation of PTM annotations and protein structures data.We so analyzed the impact of the residue modifications on the protein structures at local level. Thanks to a dedicated structure database, namely PTM-SD, a large screen of PTMs have been done and analyze at a local protein conformation levels using the structural alphabet Protein Blocks (PBs). We investigated the relation between PTMs and the backbone conformation of modified residues, of their local environment, and at the level of the complete protein structure. The two main PTM types (N-glycosylation and phosphorylation) have been studied in non-redundant datasets, and then, 4 different proteins were focused, covering 3 types of PTMs: N-glycosylation in renin endopeptidase and liver carboxylesterase, phosphorylation in cyclin-dependent kinase 2 (CDK2), and methylation in actin. We observed that PTMs could either stabilize or destabilize the backbone structure, at a local and global scale, and that these effects depend on the PTM types.

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“…Moreover, redundancy reduction to 30% maximal sequence identity implies a 6-fold decrease of the number of PDB entries. Eventually, in the large majority of the protein crystal structures deposited in the Protein Data Bank there are residues that have not been seen experimentally 31 . Since they are usually at the protein surface, it is not possible to use these structures to perform reliable analyses of the crystal packing.…”

Section: Methodsmentioning

confidence: 99%

Packing topology in crystals of proteins and small molecules: a comparison

Carugo

Blatova

Medrish

et al. 2017

Sci Rep

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We compared the topologies of protein and small molecule crystals, which have many common features – both are molecular crystals with intermolecular interactions much weaker than intramolecular interactions. They also have different features – a considerably large fraction of the volume of protein crystals is occupied by liquid water while no room is available to other molecules in small molecule crystals. We analyzed the overall and local topology and performed multilevel topological analyses (with the software package ToposPro) of carefully selected high quality sets of protein and small molecule crystal structures. Given the suboptimal packing of protein crystals, which is due the special shape and size of proteins, it would be reasonable to expect that the topology of protein crystals is different from the topology of small molecule crystals. Surprisingly, we discovered that these two types of crystalline compounds have strikingly similar topologies. This might suggest that molecular crystal formations share symmetry rules independent of molecular dimension.

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Missing strings of residues in protein crystal structures

Cited by 48 publications

References 18 publications

In silico analysis of Glanzmann variants of Calf-1 domain of αIIbβ3 integrin revealed dynamic allosteric effect

In silico analysis of Glanzmann variants of Calf-1 domain of αIIbβ3 integrin revealed dynamic allosteric effect

Investigation of the impact of PTMs on the protein backbone conformation

Packing topology in crystals of proteins and small molecules: a comparison

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