scholarly journals Surface To Surface Map Algorithm For Protein - Small Molecule Matching

2013 ◽  
pp. 7-10
Author(s):  
Neha Gupta ◽  
Megha Bajaj
Keyword(s):  
Active Sites ◽  
Tertiary Structure ◽  
Sequence Similarity ◽  
Surface Matching ◽  
Functional Surface ◽  
3 Dimensional ◽  
Shaped Surface ◽  
Ligand Binding Sites ◽  
Related Proteins ◽  
Initial Results

Current methods for protein analysis are based on either sequence similarity or comparison of overall tertiary structure. These conserved primary sequences or 3-dimensional structures may imply similar functional characteristics. However, substrate or ligand binding sites usually reside on or near protein surface, so, similarly shaped surface regions could imply similar functions. Our current work includes development of an algorithm that would allow surface matching over specific regions on related proteins with an output equal to the match percentage between two proteins. Initial results indicate that we can successfully match a family of related active sites, and find their similarly shaped surface regions. This method of surface analysis could be extended to help us understand functional surface relationship between the proteins within which there is no relationship in sequence or overall structure.

scholarly journals In silico characterization and structural modeling of bacterial metalloprotease of family M4

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rajnee Hasan ◽  
Md. Nazmul Haq Rony ◽  
Rasel Ahmed
Keyword(s):  
Drug Targets ◽  
Active Sites ◽  
Pathogenic Bacteria ◽  
Tertiary Structure ◽  
Transmembrane Helix ◽  
Confidence Score ◽  
Potential Drug ◽  
Protein Protein Interaction ◽  
Industrial Level ◽  
Potential Drug Targets

Abstract Background The M4 family of metalloproteases is comprised of a large number of zinc-containing metalloproteases. A large number of these enzymes are important virulence factors of pathogenic bacteria and therefore potential drug targets. Whereas some enzymes have potential for biotechnological applications, the M4 family of metalloproteases is known almost exclusively from bacteria. The aim of the study was to identify the structure and properties of M4 metalloprotease proteins. Results A total of 31 protein sequences of M4 metalloprotease retrieved from UniProt representing different species of bacteria have been characterized for various physiochemical properties. They were thermostable, hydrophillic protein of a molecular mass ranging from 38 to 66 KDa. Correlation on the basis of both enzymes and respective genes has also been studied by phylogenetic tree. B. cereus M4 metalloprotease (PDB ID: 1NPC) was selected as a representative species for secondary and tertiary structures among the M4 metalloprotease proteins. The secondary structure displaying 11 helices (H1-H11) is involved in 15 helix-helix interactions, while 4 β-sheet motifs composed of 15 β-strands in PDBsum. Possible disulfide bridges were absent in most of the cases. The tertiary structure of B. cereus M4 metalloprotease was validated by QMEAN4 and SAVES server (Ramachandran plot, verify 3D, and ERRAT) which proved the stability, reliability, and consistency of the tertiary structure of the protein. Functional analysis was done in terms of membrane protein topology, disease-causing region prediction, proteolytic cleavage sites prediction, and network generation. Transmembrane helix prediction showed absence of transmembrane helix in protein. Protein-protein interaction networks demonstrated that bacillolysin of B. cereus interacted with ten other proteins in a high confidence score. Five disorder regions were identified. Active sites analysis showed the zinc-binding residues—His-143, His-147, and Glu-167, with Glu-144 acting as the catalytic residues. Conclusion Moreover, this theoretical overview will help researchers to get a details idea about the protein structure and it may also help to design enzymes with desirable characteristics for exploiting them at industrial level or potential drug targets.

scholarly journals Sequence similarity of mammalian epoxide hydrolases to the bacterial haloalkane dehalogenase and other related proteins

FEBS Letters ◽  
1994 ◽  
Vol 338 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Michael Arand ◽  
David F. Grant ◽  
Jeffrey K. Beetham ◽  
Thomas Friedberg ◽  
Franz Oesch ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Haloalkane Dehalogenase ◽  
Epoxide Hydrolases ◽  
Related Proteins

Concomitant desalting and concentration of neuropeptides on a donut-shaped surface pattern for MALDI mass spectrometry

2018 ◽  
Vol 54 (45) ◽  
pp. 5688-5691 ◽  
Author(s):  
Sook Yoon ◽  
Sanghwan Park ◽  
Min Sun Kim ◽  
Chang Young Lee
Keyword(s):  
Mass Spectrometry ◽  
Saline Solution ◽  
Maldi Mass Spectrometry ◽  
Single Step ◽  
Surface Pattern ◽  
Functional Surface ◽  
Shaped Surface

We demonstrate a functional surface pattern that desalts and concentrates a highly saline solution of neuropeptides in a single step.

A novel p64-related Cl−channel: subcellular distribution and nephron segment-specific expression

1999 ◽  
Vol 276 (3) ◽  
pp. F398-F408 ◽  
Author(s):  
John C. Edwards
Keyword(s):  
Chloride Channels ◽  
Sequence Similarity ◽  
Fluid Phase ◽  
Human Kidney ◽  
Specific Expression ◽  
Proximal Tubule Cells ◽  
Sds Page ◽  
Nephron Segment ◽  
Related Proteins

Several closely related proteins that have been implicated as chloride channels of intracellular membranes have recently been described. We report here the molecular cloning and characterization of a new member of this family from human cells. On the basis of sequence similarity, we conclude that this new protein represents the human version of a previously described protein from rat brain named p64H1. The human version of p64H1 (huH1) is a 28.7-kDa protein that shows an apparent molecular mass of 31 kDa by SDS-PAGE. A single 4.5-kb message is detected on Northern blots and is present in all tissues probed. The protein is expressed in an intracellular vesicular pattern in Panc-1 cells that is distinct from the endoplasmic reticulum, fluid-phase endocytic, and transferrin-recycling compartments, but which does colocalize with caveolin. In human kidney, huH1 is highly expressed in a diffuse pattern in the apical domain of proximal tubule cells. huH1 is expressed less abundantly in a vesicular pattern in glomeruli and distal nephron.

Structural integrity of β-sheet assembly

2009 ◽  
Vol 37 (4) ◽  
pp. 671-676 ◽  
Author(s):  
Karen E. Marshall ◽  
Louise C. Serpell
Keyword(s):  
Spider Silk ◽  
Structural Integrity ◽  
Tertiary Structure ◽  
Structural Characteristics ◽  
Sequence Similarity ◽  
Underlying Structure ◽  
Β Sheet ◽  
Proteins And Peptides

The folding of a protein from a sequence of amino acids to a well-defined tertiary structure is one of the most studied and enigmatic events to take place in biological systems. Relatively recently, it has been established that some proteins and peptides are able to take on conformations other than their native fold to form long fibres known as amyloid. In vivo, these are associated with misfolding diseases, such as Alzheimer's disease, Type 2 diabetes and the amyloidoses. In vitro, peptide assembly leads to amyloid-like fibres that have high stability, resistance to degradation and high tensile strength. Remarkably, despite the lack of any obvious sequence similarity between these fibrillogenic proteins and peptides, all amyloid fibrils share common structural characteristics and their underlying structure is known as ‘cross-β’. Nature is rich in β-sheet protein assemblies such as spider silk and other ‘useful’ amyloids such as curli from Escherichia coli, where the strength of fibrils is fundamental to their function.

scholarly journals Basis for drug selectivity of plasmepsin IX and X inhibition for Plasmodium falciparum and vivax

2021 ◽  
Author(s):  
Anthony N. Hodder ◽  
Stephen Scally ◽  
Tony Triglia ◽  
Anna Ngo ◽  
Richard W. Birkinshaw ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Crystal Structures ◽  
Drug Targets ◽  
Active Sites ◽  
Drug Binding ◽  
Dual Inhibitor ◽  
3 Dimensional ◽  
Protein Substrates ◽  
Binding Cleft ◽  
Parasite Egress

Abstract Plasmepsin IX (PMIX) and X (PMX) are aspartyl proteases of Plasmodium spp. that play essential roles in parasite egress, invasion and development. Consequently, they are important drug targets for Plasmodium falciparum and P. vivax. WM4 and WM382 are potent inhibitors of PMIX and PMX that block invasion of liver and blood stages and transmission to mosquitoes. WM4 specifically inhibits PMX whilst WM382 is a dual inhibitor of PMIX and PMX. To understand the function of PMIX and PMX proteases we identified new protein substrates in P. falciparum and together with detailed kinetic analyses and structural analyses identified key molecular interactions in the active site responsible for the specificity of WM4 and WM382 inhibition. The crystal structures of PMX apo enzyme and the protease/drug complexes of PMX/WM382 and PMX/WM4 for P. falciparum and P. vivax have been solved. We show PMIX and PMX have similar substrate selectivity, however, there are distinct differences for both peptide and full-length protein substrates through differences in localised 3-dimensional structures for the enzyme substrate-binding cleft and substrate interface. The differences in affinities of WM4 and WM382 binding for PMIX and PMX map to variations in surface interactions with each protease in the S' region of the active sites. Crystal structures of PMX reveal interactions and mechanistic detail on the selectivity of drug binding which will be important for further development of clinical candidates against these important molecular targets.

scholarly journals Specificities of modeling membrane proteins using multi-template homology modeling

2020 ◽  
Author(s):  
Julia Koehler Leman ◽  
Richard Bonneau
Keyword(s):  
Membrane Proteins ◽  
Homology Modeling ◽  
De Novo ◽  
Sequence Similarity ◽  
Query Sequence ◽  
Scoring Function ◽  
Single Model ◽  
Software Suite ◽  
Structural Template ◽  
Related Proteins

AbstractStructures of membrane proteins are challenging to determine experimentally and currently represent only about 2% of the structures in the ProteinDataBank. Because of this disparity, methods for modeling membrane proteins are fewer and of lower quality than those for modeling soluble proteins. However, better expression, crystallization, and cryo-EM techniques have prompted a recent increase in experimental structures of membrane proteins, which can act as templates to predict the structure of closely related proteins through homology modeling. Because homology modeling relies on a structural template, it is easier and more accurate than fold recognition methods or de novo modeling, which are used when the sequence similarity between the query sequence and the sequence of related proteins in structural databases is below 25%. In homology modeling, a query sequence is mapped onto the coordinates of a single template and refined. With the increase in available templates, several templates often cover overlapping segments of the query sequence. Multi-template modeling can be used to identify the best template for local segments and join them into a single model. Here we provide a protocol for modeling membrane proteins from multiple templates in the Rosetta software suite. This approach takes advantage of several integrated frameworks, namely RosettaScripts, RosettaCM, and RosettaMP with the membrane scoring function.

scholarly journals Structure and specificity of novel aminopeptidase from marine sediment Archaea

2014 ◽  
Vol 70 (a1) ◽  
pp. C468-C468
Author(s):  
Karolina Michalska ◽  
Andrew Steen ◽  
Gekleng Chhor ◽  
Katlyn Fayman ◽  
Michael Endres ◽  
...  
Keyword(s):  
Active Sites ◽  
Sequence Similarity ◽  
Amino Acid Ester ◽  
Aminopeptidase Activity ◽  
Functional Screening ◽  
The Novel ◽  
Enzymatic Assays ◽  
Ocean Sediment ◽  
Recent Developments ◽  
Culture Bias

The Earth's microbial diversity remained largely unexplored until recent developments in DNA sequencing. Novel methods enabled us to access genomic information of uncultured microbial organisms and create hypotheses about their metabolic capabilities. These predictions primarily rely on the sequence similarity between a novel protein and characterized proteins. Such an approach introduces a "culture" bias: the well-understood proteins come from a set of laboratory-grown bacteria, while novel microbial proteins are obtained from a variety of environments, including the most extreme. One such niche is ocean sediment – an unexplored ecosystem that plays important roles in geochemical cycles. Single-cell genomics targeting sedimentary populations identified four new archaeons encoding putative intra- and extra-cellular proteases [1]. This discovery suggests that heterotrophic marine Archaea evolved to degrade detrital proteins and might contribute to global carbon cycling. The novel proteases share some sequence similarity with well-known protein-degrading enzymes, but generally are distant homologs. Thus, functional screening is necessary to validate sequence-based predictions. One of the proteases shares sequence similarity with S15 peptidases, cocaine esterases and α-amino acid ester hydrolases (AEH). Phylogeny indicates that the gene is of bacterial origin. Enzymatic assays reveal α-aminopeptidase activity towards dipeptides with a preference for a small, L-configured hydrophobic residue at the N-terminus. The crystal structure shows a homotetrameric, self-compartmentalizing enzyme with four independent active sites localized inside the oligomeric assembly accessible from the internal channel. The active site contains a serine protease triad (Ser-His-Asp) and a cluster of negatively charged residues that bind the N-terminal NH3+ group of the substrate molecule. Therefore, the observed activity suggests that the enzyme (designated as AP TA1) may act on di- or tri-peptides produced during extracellular degradation and subsequently imported to the cell. As a close homolog of AEHs, it is also possible that AP TA1 might participate in the synthesis of yet-to-be-discovered secondary metabolites. Supported by NIH GM094585, DOE/BER DE-AC02-06CH11357 & C-DEBI 36202823 & 157595.

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