|
| ||
|
|
||
Cationic Amino Acids (cationic + amino_acids)
Selected AbstractsThe antimicrobial activity of CCL28 is dependent on C-terminal positively-charged amino acidsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010Bin Liu Abstract Several chemokines have been shown to act as antimicrobial proteins, suggesting a direct contribution to innate immune protection. Based on the study of defensins and other antimicrobial peptides, it has been proposed that cationic amino acids in these proteins play a key role in their antimicrobial activity. The primary structure requirements necessary for the antimicrobial activity of chemokines, however, have not yet been elucidated. Using mouse CCL28, we have identified a C-terminal region of highly-charged amino acids (RKDRK) that is essential to the antimicrobial activity of the murine chemokine. Additionally, other positively-charged amino acids in the C-terminus of the protein contribute to the observed antimicrobial effect. Charge reversal and deletion mutations support our hypothesis that C-terminal positively-charged amino acids are essential for the antimicrobial activity of CCL28. Results also demonstrate that although the C-terminal region of the chemokine is essential, it is not sufficient for full antimicrobial activity of CCL28. [source] Human solute carrier SLC6A14 is the ,-alanine carrierTHE JOURNAL OF PHYSIOLOGY, Issue 17 2008Catriona M. H. Anderson The ,-alanine carrier was characterized functionally in the 1960s to 1980s at the luminal surface of the ileal mucosal wall and is a Na+ - and Cl, -dependent transporter of a number of essential and non-essential cationic and dipolar amino acids including lysine, arginine and leucine. ,-Alanine carrier-like function has not been demonstrated by any solute carrier transport system identified at the molecular level. A series of experiments were designed to determine whether solute carrier SLC6A14 is the molecular correlate of the intestinal ,-alanine carrier, perhaps the last of the classical intestinal amino acid transport systems to be identified at the molecular level. Following expression of the human SLC6A14 transporter in Xenopus laevis oocytes, the key functional characteristics of the ,-alanine carrier, identified previously in situ in ileum, were demonstrated for the first time. The transport system is both Na+ and Cl, dependent, can transport non-,-amino acids such as ,-alanine with low affinity, and has a higher affinity for dipolar and cationic amino acids such as leucine and lysine. N -methylation of its substrates reduces the affinity for transport. These observations confirm the hypothesis that the SLC6A14 gene encodes the transport protein known as the ,-alanine carrier which, due to its broad substrate specificity, is likely to play an important role in absorption of essential nutrients and drugs in the distal regions of the human gastrointestinal tract. [source] Disperse distribution of cationic amino acids on hydrophilic surface of helical wheel enhances antimicrobial peptide activityBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010Young Soo Kim Abstract The antimicrobial action of amphipathic antimicrobial peptides (AMPs) generally depends on perturbation of the bacterial membrane via electrostatic interactions promoting initial binding to the surface and hydrophobic interactions for pore formation into the membrane. Several studies have focused on the structure,activity relationship (SAR) of AMPs by modulation of structural parameters. However, modulation of one parameter commonly induces simultaneous changes in other parameters, making it difficult to investigate the specific influence of a single variable. In the present work, we investigated the distribution effect of cationic amino acids on the hydrophilic surface of the helical wheel using model AMPs composed of only lysine (K) and leucine (L) as representative cationic and hydrophobic residues, respectively, under conditions in which other parameters are fixed. Based on SAR analyses of ,-helical KL model AMPs displaying different cationic distributions, we propose that the dispersity of cationic amino acids on the hydrophilic surface is a factor that contributes to the antimicrobial activity of AMP. Moreover, antimicrobial activity is enhanced by rearrangement of cationic amino acids to promote dispersed distribution. We confirmed the cationic distribution effect using natural AMP-derived ,-helical CRAMP18 and its analogs. Our data show that accumulation of lysine shifts in the CRAMP18 analog leads to higher dispersion, and subsequently to improved antimicrobial activity. Therefore, we propose that the cationic distribution effect can be applied for the rational redesign of amino acid sequences to improve the antimicrobial activities of natural ,-helical AMPs, in combination with regulation of other known structural parameters. Biotechnol. Bioeng. 2010;107: 216,223. © 2010 Wiley Periodicals, Inc. [source] | ||||||||||