ClusPro: Performance in CAPRI rounds 6–11 and the new server

Comeau, Stephen R.; Kozakov, Dima; Brenke, Ryan; Shen, Yang; Beglov, Dmitri; Vajda, Sándor

doi:10.1002/prot.21795

Cited by 77 publications

(66 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If a similar complex were to form in solution with heme in only the donor molecule, this model would support heme transfer from Tyr of the donor to Tyr of the receptor, possibly with a bis-Tyr heme intermediate. To examine the potential to form these complexes in solution, we used the proteinprotein complex modeling server ClusPro 45,46 to predict unbiased optimal IsdB-N2-IsdA-N1 and IsdA-N1-IsdC-N1 complexes. The heme ligand was not modeled at the interface in ClusPro, but again, the top solutions were strikingly similar to the interactions observed in crystal packing (Fig.…”

Section: Discussionmentioning

confidence: 99%

Iron-Coordinating Tyrosine Is a Key Determinant of NEAT Domain Heme Transfer

Grigg

Mao

Murphy

2011

Journal of Molecular Biology

View full text Add to dashboard Cite

In humans, heme iron is the most abundant iron source, and bacterial pathogens such as Staphylococcus aureus acquire it for growth. IsdB of S. aureus acquires Fe(III)-protoporphyrin IX (heme) from hemoglobin for transfer to IsdC via IsdA. These three cell-wall-anchored Isd (iron-regulated surface determinant) proteins contain conserved NEAT (near iron transport) domains. The purpose of this work was to delineate the mechanism of heme binding and transfer between the NEAT domains of IsdA, IsdB, and IsdC using a combination of structural and spectroscopic studies. X-ray crystal structures of IsdA NEAT domain (IsdA-N1) variants reveal that removing the native heme-iron ligand Tyr166 is compensated for by iron coordination by His83 on the distal side and that no single mutation of distal loop residues is sufficient to perturb the IsdA-heme complex. Also, alternate heme-iron coordination was observed in structures of IsdA-N1 bound to reduced Fe(II)-protoporphyrin IX and Co(III)-protoporphyrin IX. The IsdA-N1 structural data were correlated with heme transfer kinetics from the NEAT domains of IsdB and IsdC. We demonstrated that the NEAT domains transfer heme at rates comparable to full-length proteins. The second-order rate constant for heme transfer from IsdA-N1 was modestly affected (<2-fold) by the IsdA variants, excluding those at Tyr166. Substituting Tyr166 with Ala or Phe changed the reaction mechanism to one with two observable steps and decreased observed rates >15-fold (to 100-fold excess IsdC). We propose a heme transfer model wherein NEAT domain complexes pass heme iron directly from an iron-coordinating Tyr of the donor protein to the homologous Tyr residues of the acceptor protein.

show abstract

Section: Discussionmentioning

confidence: 99%

Iron-Coordinating Tyrosine Is a Key Determinant of NEAT Domain Heme Transfer

Grigg

Mao

Murphy

2011

Journal of Molecular Biology

View full text Add to dashboard Cite

show abstract

“…Thus, an all-atom model was initialized using 1X18 as a template, optimized using 1,000 iterations of variable target function method with conjugate gradients, and then refined using molecular dynamics with simulated annealing, all of which was achieved with the program MODELLER (62). A crystal structure of E. coli YbeY (PDB accession code 1XM5) was rigidly docked to the all-atom model of limited 30S-Era structure using a webserver ClusPro (63). The top 10 models were collected for each of four sets of differently weighted sum of energy terms such as electrostatics, van der Waals, and knowledge-based statistical potentials derived from known protein-protein interactions.…”

Section: Methodsmentioning

confidence: 99%

Identification of YbeY-Protein Interactions Involved in 16S rRNA Maturation and Stress Regulation in Escherichia coli

Vercruysse

Köhrer

Shen³

et al. 2016

mBio

Self Cite

View full text Add to dashboard Cite

YbeY is part of a core set of RNases in Escherichia coli and other bacteria. This highly conserved endoribonuclease has been implicated in several important processes such as 16S rRNA 3′ end maturation, 70S ribosome quality control, and regulation of mRNAs and small noncoding RNAs, thereby affecting cellular viability, stress tolerance, and pathogenic and symbiotic behavior of bacteria. Thus, YbeY likely interacts with numerous protein or RNA partners that are involved in various aspects of cellular physiology. Using a bacterial two-hybrid system, we identified several proteins that interact with YbeY, including ribosomal protein S11, the ribosome-associated GTPases Era and Der, YbeZ, and SpoT. In particular, the interaction of YbeY with S11 and Era provides insight into YbeY’s involvement in the 16S rRNA maturation process. The three-way association between YbeY, S11, and Era suggests that YbeY is recruited to the ribosome where it could cleave the 17S rRNA precursor endonucleolytically at or near the 3′ end maturation site. Analysis of YbeY missense mutants shows that a highly conserved beta-sheet in YbeY—and not amino acids known to be important for YbeY’s RNase activity—functions as the interface between YbeY and S11. This protein-interacting interface of YbeY is needed for correct rRNA maturation and stress regulation, as missense mutants show significant phenotypic defects. Additionally, structure-based in silico prediction of putative interactions between YbeY and the Era-30S complex through protein docking agrees well with the in vivo results.

show abstract

“…The SLAPI 3D models selected previously were docked with a proteinase A crystal structure (PDB ID: 1dpj, after removal of the chain corresponding to the IA 3 inhibitor), using the web server ClusPro version 2.0 (http://nrc.bu.edu/ cluster) [38]. The fully automated docking server ClusPro was executed with the default parameters and, as a result, it provided four sets of models based on four different coefficients: Balanced, Electrostatic, Hydrophobic and WdV+Electrostatic [39].…”

Section: Protein-protein Dockingmentioning

confidence: 99%

Predicting functional residues of the Solanum lycopersicum aspartic protease inhibitor (SLAPI) by combining sequence and structural analysis with molecular docking

et al. 2011

View full text Add to dashboard Cite

The Solanum lycopersicum aspartic protease inhibitor (SLAPI), which belongs to the STI-Kunitz family, is an effective inhibitor of the aspartic proteases human cathepsin D and Saccharomyces proteinase A. However, in contrast with the large number of studies on the inhibition mechanism of the serine proteases by the STI-Kunitz inhibitors, the structural aspects of the inhibition mechanism of aspartic proteases from this family of inhibitors are poorly understood. In the present study, we have combined sequence and structural analysis methods with protein-protein docking to gain a better understanding of the SLAPI inhibition mechanism of the proteinase A. The results suggest that: i) SLAPI loop L9 may be involved in the inhibitor interaction with the proteinase A´s active site, and ii) the residues I144, V148, L149, P151, F152 and R154 are implicated in the difference in the potency shown previously by SLAPI and another STI-Kunitz inhibitor isolated from Solanum tuberosum to inhibit proteinase A. These results will be useful in the design of site directed mutagenesis experiments to understand more thoroughly the aspartic protease inhibition mechanism of SLAPI and other related STI-Kunitz inhibitors.

show abstract

ClusPro: Performance in CAPRI rounds 6–11 and the new server

Cited by 77 publications

References 27 publications

Iron-Coordinating Tyrosine Is a Key Determinant of NEAT Domain Heme Transfer

Iron-Coordinating Tyrosine Is a Key Determinant of NEAT Domain Heme Transfer

Identification of YbeY-Protein Interactions Involved in 16S rRNA Maturation and Stress Regulation in Escherichia coli

Predicting functional residues of the Solanum lycopersicum aspartic protease inhibitor (SLAPI) by combining sequence and structural analysis with molecular docking

Contact Info

Product

Resources

About