ProtCID: a data resource for structural information on protein interactions

Xu, Qifang; Dunbrack, Roland L.

doi:10.1038/s41467-020-14301-4

Cited by 44 publications

(43 citation statements)

References 66 publications

(73 reference statements)

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“…We previously reported that a form of MDM2-FL migrates very close to MDM2-C on SDS-PAGE gels 19 and therefore this verification of the differential antibody detection was very important. We used the Protein Common Interface Database (ProtCID) 27 to analyze MDM2-C RING interactions and found an interaction with the E2 ubiquitin-conjugating enzyme UbcH5B and ubiquitin (Figure 1D). This predicted MDM2-C RING interactions with the E2 ubiquitin-conjugating enzyme (UbcH5B) and ubiquitin (Ub) by ProtCID (Protein Common Interface Database).…”

Section: Purified Mdm2-fl and Mdm2-c Are Recognized By Distinct Monoclonal Antibodiesmentioning

confidence: 99%

“…This predicted MDM2-C RING interactions with the E2 ubiquitin-conjugating enzyme (UbcH5B) and ubiquitin (Ub) by ProtCID (Protein Common Interface Database). 27 The amino acid sequence of MDM2-C was entered and three PFAM IDs were identified: zf-RanBP (Zn-finger in Ran binding protein and others) aa: 129-158; Pinin_SDK_N (pinin/SDK conserved region) aa: 147-255; and zf-C3HC4 (RING finger) aa: 264-315.…”

Section: Purified Mdm2-fl and Mdm2-c Are Recognized By Distinct Monoclonal Antibodiesmentioning

confidence: 99%

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<p>MDM2-C Functions as an E3 Ubiquitin Ligase</p>

Kim

Lee

Xiao

et al. 2020

CMAR

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Background Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase that is over-expressed in many cancers and regulates target proteins through ubiquitination. Full-length MDM2 (MDM2-FL) is best known for targeting wild-type p53 for degradation by the proteasome, but the functions of the many splice variants of MDM2 are under-explored. The three well-studied alternative MDM2 isoforms are MDM2-A/ALT2, MDM2-B/ALT1, and MDM2-C/ALT3. MDM2-A and MDM2-B are capable of down-regulating MDM2-FL activity and have transforming activity in cancers with mutant p53. The MDM2 isoform MDM2-C is over-expressed in breast cancer and correlates with decreased survival in the context of mutant p53 expression. Therefore, MDM2-C requires further study to determine if it has biochemical activities similar to MDM2-FL. Hypothesis: We hypothesized that like MDM2-FL, the MDM2-C isoform (lacking exons 5–9 and containing a full C-terminal RING finger sequence) would maintain E3 ubiquitin ligase activity. Materials and Methods In order to explore the biochemical function of MDM2-C, we used an in vitro ubiquitination assay and a glutaraldehyde cross-linking assay. Results Here we report, for the first time, that MDM2-C has E3 auto-ubiquitin ligase activity, which can promote ubiquitination of wild-type p53 and mutant p53 R273H, and also can form a protein–protein interaction with p53 proteins. Conclusion This information strongly positions MDM2-C as a protein with biochemical activities that may explain the varied outcomes observed in patients with high-level expression of MDM2-C in the presence of wild-type p53 versus mutant p53.

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Section: Purified Mdm2-fl and Mdm2-c Are Recognized By Distinct Monoclonal Antibodiesmentioning

confidence: 99%

Section: Purified Mdm2-fl and Mdm2-c Are Recognized By Distinct Monoclonal Antibodiesmentioning

confidence: 99%

<p>MDM2-C Functions as an E3 Ubiquitin Ligase</p>

Kim

Lee

Xiao

et al. 2020

CMAR

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“…It provides clusters of interfaces of full-length protein chains and functional domains as a means of identifying biological assemblies, showing information on four types of interactions: protein-protein interactions at the chain level, protein-protein interactions at the domain level, domain-peptide interactions, and also the interactions of domains with nucleic acids and ligands. Within the ProtCID server, the PDBfam database contains 8636 protein domain families (Pfams) present in the PDB (Xu and Dunbrack, 2020).…”

Section: Ppi Resourcesmentioning

confidence: 99%

Mapping, Structure and Modulation of PPI

et al. 2021

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Because of the key relevance of protein–protein interactions (PPI) in diseases, the modulation of protein-protein complexes is of relevant clinical significance. The successful design of binding compounds modulating PPI requires a detailed knowledge of the involved protein-protein system at molecular level, and investigation of the structural motifs that drive the association of the proteins at the recognition interface. These elements represent hot spots of the protein binding free energy, define the complex lifetime and possible modulation strategies. Here, we review the advanced technologies used to map the PPI involved in human diseases, to investigate the structure-function features of protein complexes, and to discover effective ligands that modulate the PPI for therapeutic intervention.

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“…The individual component of the target complex was either an experimental structure or good quality theoretical model (built by homology or ab initio ). Only those proteins for which reliable biological assembly information could be determined were selected, using the ProtCID server [ 71 ]. This resulted in 4 CAPRI targets (from the 332 host–viral interactions detected experimentally by Gordon et al.…”

Section: Capri Covid19 Open Science Initiativementioning

confidence: 99%

The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies

Waman¹,

Sen²,

Váradi³

et al. 2020

Briefings in Bioinformatics

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SARS-CoV-2 is the causative agent of COVID-19, the ongoing global pandemic. It has posed a worldwide challenge to human health as no effective treatment is currently available to combat the disease. Its severity has led to unprecedented collaborative initiatives for therapeutic solutions against COVID-19. Studies resorting to structure-based drug design for COVID-19 are plethoric and show good promise. Structural biology provides key insights into 3D structures, critical residues/mutations in SARS-CoV-2 proteins, implicated in infectivity, molecular recognition and susceptibility to a broad range of host species. The detailed understanding of viral proteins and their complexes with host receptors and candidate epitope/lead compounds is the key to developing a structure-guided therapeutic design. Since the discovery of SARS-CoV-2, several structures of its proteins have been determined experimentally at an unprecedented speed and deposited in the Protein Data Bank. Further, specialized structural bioinformatics tools and resources have been developed for theoretical models, data on protein dynamics from computer simulations, impact of variants/mutations and molecular therapeutics. Here, we provide an overview of ongoing efforts on developing structural bioinformatics tools and resources for COVID-19 research. We also discuss the impact of these resources and structure-based studies, to understand various aspects of SARS-CoV-2 infection and therapeutic development. These include (i) understanding differences between SARS-CoV-2 and SARS-CoV, leading to increased infectivity of SARS-CoV-2, (ii) deciphering key residues in the SARS-CoV-2 involved in receptor–antibody recognition, (iii) analysis of variants in host proteins that affect host susceptibility to infection and (iv) analyses facilitating structure-based drug and vaccine design against SARS-CoV-2.

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ProtCID: a data resource for structural information on protein interactions

Cited by 44 publications

References 66 publications

<p>MDM2-C Functions as an E3 Ubiquitin Ligase</p>

<p>MDM2-C Functions as an E3 Ubiquitin Ligase</p>

Mapping, Structure and Modulation of PPI

The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies

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