scholarly journals Structure and function of an Antiporter

2014 ◽  
Vol 70 (a1) ◽  
pp. C1046-C1046
Author(s):  
David Wöhlert ◽  
Werner Kühlbrandt ◽  
Özkan Yildiz
Keyword(s):  
Membrane Proteins ◽  
Membrane Transport ◽  
Crystal Structures ◽  
Drug Targets ◽  
Transport Proteins ◽  
Ph Homeostasis ◽  
Secondary Transporter ◽  
Target Membrane ◽  
Approved Drugs ◽  
And Function

Membrane proteins are essential to transport molecules across biological membranes. This gateway task makes them important drug targets. About 60% of all approved drugs target membrane proteins. Transport of ions across membranes is essential for every cell to maintain physiological salt concentrations and to keep pH homeostasis. In the past years X-Ray structures of various secondary transporters have provided insight into the mechanisms of membrane transport. However, difficulties in expression, purification and crystallization of membrane proteins still restrict the number of available structures. For well-characterized secondary transporters such as LeuT (1), BetP (2) and Ca2+/H+-exchangers (3) crystal structures in different conformations and substrate binding states have been obtained. However, for many important classes of transport proteins, detailed structures are urgently needed to understand their mechanism of action and to guide drug development. We report crystal structures of 2 homologues of a new secondary transporter in different states, with or without substrate bound. These structures shed light on the transport mechanism of this important class of membrane transport proteins.

Phylogeny as a guide to structure and function of membrane transport proteins (Review)

2004 ◽  
Vol 21 (3) ◽  
pp. 171-181 ◽  
Author(s):  
Abraham B. Chang ◽  
Ron Lin ◽  
W. Keith Studley ◽  
Can V. Tran ◽  
Milton H. Saier, Jr
Keyword(s):  
Membrane Transport ◽  
Transport Proteins ◽  
Structure And Function ◽  
Membrane Transport Proteins ◽  
And Function

scholarly journals Stress-Responsive Systems Set Specific Limits to the Overproduction of Membrane Proteins in Bacillus subtilis

2009 ◽  
Vol 75 (23) ◽  
pp. 7356-7364 ◽  
Author(s):  
Jessica C. Zweers ◽  
Thomas Wiegert ◽  
Jan Maarten van Dijl
Keyword(s):  
Bacillus Subtilis ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Drug Targets ◽  
Protein Production ◽  
Cell Envelope ◽  
Regulatory System ◽  
Interesting Candidate ◽  
High Level ◽  
And Function

ABSTRACT Essential membrane proteins are generally recognized as relevant potential drug targets due to their exposed localization in the cell envelope. Unfortunately, high-level production of membrane proteins for functional and structural analyses is often problematic. This is mainly due to their high overall hydrophobicity. To develop new concepts for membrane protein overproduction, we investigated whether the biogenesis of overproduced membrane proteins is affected by stress response-related proteolytic systems in the membrane. For this purpose, the well-established expression host Bacillus subtilis was used to overproduce eight essential membrane proteins from B. subtilis and Staphylococcus aureus. The results show that the σW regulon (responding to cell envelope perturbations) and the CssRS two-component regulatory system (responding to unfolded exported proteins) set critical limits to membrane protein production in large quantities. The identified sigW or cssRS mutant B. subtilis strains with significantly improved capacity for membrane protein production are interesting candidate expression hosts for fundamental research and biotechnological applications. Importantly, our results pinpoint the interdependent expression and function of membrane-associated proteases as key parameters in bacterial membrane protein production.

scholarly journals Identification of Potential Drug Targets and Prediction of the Potential Impact of High Risk Non Synonymous Single Nucleotide Polymorphism in SARS-CoV-2 3C like Proteinase (3CLpro): A Computational Approach

2020 ◽  
Author(s):  
Sahar Elbager ◽  
abdelrahman hamza ◽  
Afra M. Al Bkrye ◽  
Asia M. Alrashied ◽  
Entisar N. M. Ali ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Drug Binding ◽  
Snp Analysis ◽  
Potential Drug ◽  
Full Genome Sequencing ◽  
Drug Binding Site ◽  
Adme Properties ◽  
Approved Drugs ◽  
And Function

On January 2020, a new coronavirus (officially named SARS-CoV-2) was associated with alarming outbreak of a pneumonia-like illness, which was later named by the WHO as COVID-19, originating from Wuhan City, China. Although many clinical studies involving antiviral and immunomodulatory drug treatments for SARS-CoV-2 all without reported results, no approved drugs have been found to effectively inhibit the virus so far. Full genome sequencing of the virus was done, and uploaded to be freely available for the world scientists to explore. A promising target for SARS-CoV-2 drug design is a chymotrypsin-like cysteine protease (3CLpro), a main protease responsible for the replication and maturation of functional proteins in the life cycle of the SARS coronavirus. Here we aim to explore SARS-CoV-2 3CLpro as possible drug targets based on ligand- protein interactions. In addition, ADME properties of the ligands were also analyzed to predict their drug likeliness. The results revealed Out of 9 ligands, 8 ligands (JFM, X77, RZG, HWH, T8A, 0EN, PEPTIDE and DMS) showed best ADME properties. These findings suggest that these ligands can be used as potential molecules for developing potent inhibitors against SARS-CoV-2 3CLpro, which could be helpful in inhibiting the propagation of the COVID-19. Furthermore, 10 potential amino acids residues were recognized as potential drug binding site (THR25, HIS41, GLY143, SER144, CYS145, MET165, GLU166, GLN189, ASP295 and ARG298). All those amino acid residues were subjected to missense SNP analysis were recognized to affect the structure and function of the protein. These characteristics provide them the promising to be target sites for the fresh generation inhibitors to work with and overcome drug resistance. These findings would be beneficial for the drug development for inhibiting SARS-CoV-2 3CLpro hence assisting the pharmacogenomics effort to manage the infection. of SARS-CoV-2.

scholarly journals Identification of Potential Drug Targets and Prediction of the Potential Impact of High Risk Non Synonymous Single Nucleotide Polymorphism in SARS-CoV-2 3C like Proteinase (3CLpro): A Computational Approach

2020 ◽  
Author(s):  
Sahar Elbager ◽  
abdelrahman hamza ◽  
Afra M. Al Bkrye ◽  
Asia M. Alrashied ◽  
Entisar N. M. Ali ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Drug Targets ◽  
Drug Binding ◽  
Snp Analysis ◽  
Potential Drug ◽  
Full Genome Sequencing ◽  
Drug Binding Site ◽  
Adme Properties ◽  
Approved Drugs ◽  
And Function

On January 2020, a new coronavirus (officially named SARS-CoV-2) was associated with alarming outbreak of a pneumonia-like illness, which was later named by the WHO as COVID-19, originating from Wuhan City, China. Although many clinical studies involving antiviral and immunomodulatory drug treatments for SARS-CoV-2 all without reported results, no approved drugs have been found to effectively inhibit the virus so far. Full genome sequencing of the virus was done, and uploaded to be freely available for the world scientists to explore. A promising target for SARS-CoV-2 drug design is a chymotrypsin-like cysteine protease (3CLpro), a main protease responsible for the replication and maturation of functional proteins in the life cycle of the SARS coronavirus. Here we aim to explore SARS-CoV-2 3CLpro as possible drug targets based on ligand- protein interactions. In addition, ADME properties of the ligands were also analyzed to predict their drug likeliness. The results revealed Out of 9 ligands, 8 ligands (JFM, X77, RZG, HWH, T8A, 0EN, PEPTIDE and DMS) showed best ADME properties. These findings suggest that these ligands can be used as potential molecules for developing potent inhibitors against SARS-CoV-2 3CLpro, which could be helpful in inhibiting the propagation of the COVID-19. Furthermore, 10 potential amino acids residues were recognized as potential drug binding site (THR25, HIS41, GLY143, SER144, CYS145, MET165, GLU166, GLN189, ASP295 and ARG298). All those amino acid residues were subjected to missense SNP analysis were recognized to affect the structure and function of the protein. These characteristics provide them the promising to be target sites for the fresh generation inhibitors to work with and overcome drug resistance. These findings would be beneficial for the drug development for inhibiting SARS-CoV-2 3CLpro hence assisting the pharmacogenomics effort to manage the infection. of SARS-CoV-2.

scholarly journals Therapeutic Nanobodies Targeting Cell Plasma Membrane Transport Proteins: A High-Risk/High-Gain Endeavor

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 63
Author(s):  
Raf Van Campenhout ◽  
Serge Muyldermans ◽  
Mathieu Vinken ◽  
Nick Devoogdt ◽  
Timo W.M. De Groof
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Membrane Transport ◽  
Transport Proteins ◽  
Therapeutic Drug ◽  
Cell Plasma Membrane ◽  
Plasma Membrane Proteins ◽  
Altered Expression ◽  
Membrane Transport Proteins ◽  
Cell Plasma

Cell plasma membrane proteins are considered as gatekeepers of the cell and play a major role in regulating various processes. Transport proteins constitute a subclass of cell plasma membrane proteins enabling the exchange of molecules and ions between the extracellular environment and the cytosol. A plethora of human pathologies are associated with the altered expression or dysfunction of cell plasma membrane transport proteins, making them interesting therapeutic drug targets. However, the search for therapeutics is challenging, since many drug candidates targeting cell plasma membrane proteins fail in (pre)clinical testing due to inadequate selectivity, specificity, potency or stability. These latter characteristics are met by nanobodies, which potentially renders them eligible therapeutics targeting cell plasma membrane proteins. Therefore, a therapeutic nanobody-based strategy seems a valid approach to target and modulate the activity of cell plasma membrane transport proteins. This review paper focuses on methodologies to generate cell plasma membrane transport protein-targeting nanobodies, and the advantages and pitfalls while generating these small antibody-derivatives, and discusses several therapeutic nanobodies directed towards transmembrane proteins, including channels and pores, adenosine triphosphate-powered pumps and porters.

Crystal Structures of Fragments D and Double-D from Fibrinogen and Fibrin

1999 ◽  
Vol 82 (08) ◽  
pp. 271-276 ◽  
Author(s):  
Glen Spraggon ◽  
Stephen Everse ◽  
Russell Doolittle
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Crystal Structures ◽  
Structure And Function ◽  
X Ray ◽  
Long Period ◽  
And Function

IntroductionAfter a long period of anticipation,1 the last two years have witnessed the first high-resolution x-ray structures of fragments from fibrinogen and fibrin.2-7 The results confirmed many aspects of fibrinogen structure and function that had previously been inferred from electron microscopy and biochemistry and revealed some unexpected features. Several matters have remained stubbornly unsettled, however, and much more work remains to be done. Here, we review several of the most significant findings that have accompanied the new x-ray structures and discuss some of the problems of the fibrinogen-fibrin conversion that remain unresolved. * Abbreviations: GPR—Gly-Pro-Arg-derivatives; GPRPam—Gly-Pro-Arg-Pro-amide; GHRPam—Gly-His-Arg-Pro-amide

How Do Lipids Affect the Structure and Function of Integral Membrane Proteins

2012 ◽  
Vol 28 (11) ◽  
pp. 866
Author(s):  
Jie HENG ◽  
Yan WU ◽  
Xianping WANG ◽  
Kai ZHANG
Keyword(s):  
Membrane Proteins ◽  
Structure And Function ◽  
Integral Membrane Proteins ◽  
And Function

Molecular characterization of SARS-CoV-2

2020 ◽  
Vol 20 ◽  
Author(s):  
Miribane Dërmaku-Sopjani ◽  
Mentor Sopjani
Keyword(s):  
Public Health ◽  
Drug Targets ◽  
Virus Genome ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Therapeutic Drugs ◽  
New Public Health ◽  
New Public ◽  
And Function

Abstract:: The coronavirus disease 2019 (COVID-19) is currently a new public health crisis threatening the world. This pandemic disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus has been reported to be originated in bats and by yet unknown intermediary animals were transmitted to humans in China 2019. The SARSCoV- 2 spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERSCoV) but has reduced fatality. At present, the SARS-CoV-2 has caused about a 1.16 million of deaths with more than 43.4 million confirmed cases worldwide, resulting in a serious threat to public health globally with yet uncertain impact. The disease is transmitted by inhalation or direct contact with an infected person. The incubation period ranges from 1 to 14 days. COVID-19 is accompanied by various symptoms, including cough, fatigue. In most people the disease is mild, but in some other people, such as in elderly and people with chronic diseases, it may progress from pneumonia to a multi-organ dysfunction. Many people are reported asymptomatic. The virus genome is sequenced, but new variants are reported. Numerous biochemical aspects of its structure and function are revealed. To date, no clinically approved vaccines and/or specific therapeutic drugs are available to prevent or treat the COVID-19. However, there are reported intensive researches on the SARSCoV- 2 to potentially identify vaccines and/or drug targets, which may help to overcome the disease. In this review, we discuss recent advances in understanding the molecular structure of SARS-CoV-2 and its biochemical characteristics.

Sign in / Sign up

Export Citation Format

Share Document