2l5m
From Proteopedia
(Difference between revisions)
| Line 2: | Line 2: | ||
<StructureSection load='2l5m' size='340' side='right' caption='[[2l5m]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='2l5m' size='340' side='right' caption='[[2l5m]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[2l5m]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5M OCA]. <br> | + | <table><tr><td colspan='2'>[[2l5m]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5M OCA]. <br> |
| - | <b>[[Non-Standard_Residue|NonStd Res:]]</b> <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>< | + | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | <b>[[Related_structure|Related:]]</b> [[2k6o|2k6o]]< | + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2k6o|2k6o]]</td></tr> |
| - | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span>< | + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l5m RCSB], [http://www.ebi.ac.uk/pdbsum/2l5m PDBsum]</span>< | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l5m RCSB], [http://www.ebi.ac.uk/pdbsum/2l5m PDBsum]</span></td></tr> |
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Human cathelicidin LL-37 is a critical cationic antimicrobial peptide for host defense against infection, immune modulation, and wound healing. This article elucidates the functional roles of the cationic side chains of the major antimicrobial region of LL-37, corresponding to residues 17-32 (designated GF-17). Antimicrobial assays, killing kinetics studies, and vesicle leakage experiments all indicate that a conversion of lysines to arginines affected the ability of the peptide to kill the Gram-positive Staphylococcus aureus USA300 strain. Alanine scanning experiments show that S. aureus is less sensitive to the single cationic residue mutation of GF-17, whereas Escherichia coli is more susceptible. Among the five cationic residues, R23 appears to be somewhat important in killing S. aureus. However, R23 and K25 of GF-17 are of prime importance in killing Gram-negative E. coli. In particular, R23 is essential for (1) rapid recognition; (2) permeation of the E. coli outer membrane; (3) clustering of anionic lipids in a membrane system mimicking the E. coli inner membrane; and (4) membrane disruption. Bacterial aggregation (i.e. rapid recognition via charge neutralization) is the first step of the peptide action. Structurally, R23 is located in the interface (i.e. the first action layer) ideal for the above interactions. In contrast, residues K18, R19, and R29 are on the hydrophilic surface of the amphipathic helix and only play a secondary role. Mapping the functional spectrum of cationic residues of GF-17 provides a solid basis for engineering bacteria-specific antimicrobials using this highly potent template. | Human cathelicidin LL-37 is a critical cationic antimicrobial peptide for host defense against infection, immune modulation, and wound healing. This article elucidates the functional roles of the cationic side chains of the major antimicrobial region of LL-37, corresponding to residues 17-32 (designated GF-17). Antimicrobial assays, killing kinetics studies, and vesicle leakage experiments all indicate that a conversion of lysines to arginines affected the ability of the peptide to kill the Gram-positive Staphylococcus aureus USA300 strain. Alanine scanning experiments show that S. aureus is less sensitive to the single cationic residue mutation of GF-17, whereas Escherichia coli is more susceptible. Among the five cationic residues, R23 appears to be somewhat important in killing S. aureus. However, R23 and K25 of GF-17 are of prime importance in killing Gram-negative E. coli. In particular, R23 is essential for (1) rapid recognition; (2) permeation of the E. coli outer membrane; (3) clustering of anionic lipids in a membrane system mimicking the E. coli inner membrane; and (4) membrane disruption. Bacterial aggregation (i.e. rapid recognition via charge neutralization) is the first step of the peptide action. Structurally, R23 is located in the interface (i.e. the first action layer) ideal for the above interactions. In contrast, residues K18, R19, and R29 are on the hydrophilic surface of the amphipathic helix and only play a secondary role. Mapping the functional spectrum of cationic residues of GF-17 provides a solid basis for engineering bacteria-specific antimicrobials using this highly potent template. | ||
| Line 13: | Line 15: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:46, 1 May 2014
Solution structure of GF-17 in complex with micelles
| |||||||||||
