1. The changing faces of Streptococcus antigen I/II polypeptide family adhesins
L Jeannine Brady, Sarah E Maddocks, Matthew R Larson, Nina Forsgren, Karina Persson, Champion C Deivanayagam, Howard F Jenkinson Mol Microbiol. 2010 Jul;77(2):276-86. doi: 10.1111/j.1365-2958.2010.07212.x. Epub 2010 May 24.
Streptococcus mutans antigen I/II (AgI/II) protein was one of the first cell wall-anchored adhesins identified in Gram-positive bacteria. It mediates attachment of S. mutans to tooth surfaces and has been a focus for immunization studies against dental caries. The AgI/II family polypeptides recognize salivary glycoproteins, and are also involved in biofilm formation, platelet aggregation, tissue invasion and immune modulation. The genes encoding AgI/II family polypeptides are found among Streptococcus species indigenous to the human mouth, as well as in Streptococcus pyogenes, S. agalactiae and S. suis. Evidence of functionalities for different regions of the AgI/II proteins has emerged. A sequence motif within the C-terminal portion of Streptococcus gordonii SspB (AgI/II) is bound by Porphyromonas gingivalis, thus promoting oral colonization by this anaerobic pathogen. The significance of other epitopes is now clearer following resolution of regional crystal structures. A new picture emerges of the central V (variable) region, predicted to contain a carbohydrate-binding trench, being projected from the cell surface by a stalk formed by an unusual association between an N-terminal alpha-helix and a C-terminal polyproline helix. This presentation mode might be important in determining functional conformations of other Gram-positive surface proteins that have adhesin domains flanked by alpha-helical and proline-rich regions.
2. Matrix metalloproteinases: drug targets for myocardial infarction
Andriy Yabluchanskiy, Yaojun Li, Robert J Chilton, Merry L Lindsey Curr Drug Targets. 2013 Mar;14(3):276-86.
Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. Rapid advances in the treatment of acute MI have significantly improved short-term outcomes in patients, due in large part to successes in preventing myocardial cell death and limiting infarct area during the time of ischemia and subsequent reperfusion. Matrix metalloproteases (MMPs) play key roles in post-MI cardiac remodeling and in the development of adverse outcomes. This review highlights the importance of MMPs in the injury and remodeling response of the left ventricle and also discusses their potential as therapeutic targets Additional pre-clinical and clinical research is needed to further investigate and understand the cardioprotective effects of MMPs inhibitors.
3. Impact of the Recent Mouse P-Glycoprotein Structure for Structure-Based Ligand Design
Freya Klepsch, Gerhard F Ecker Mol Inform. 2010 Apr 12;29(4):276-86. doi: 10.1002/minf.201000017. Epub 2010 Apr 20.
P-Glycoprotein (P-gp), a transmembrane, ATP-dependent drug efflux transporter, has attracted considerable interest both with respect to its role in tumour cell multidrug resistance and in absorption-distribution and elimination of drugs. Although known since more than 30 years, the understanding of the molecular basis of drug/transporter interaction is still limited, which is mainly due to the lack of structural information available. However, within the past decade X-ray structures of several bacterial homologues as well as very recently also of mouse P-gp have become available. Within this review we give an overview on the current status of structural information available and on its impact for structure-based drug design.
