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| - | [[Image:2hky.jpg|left|200px]] | |
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| - | {{Structure
| + | ==NMR solution structure of human RNase 7== |
| - | |PDB= 2hky |SIZE=350|CAPTION= <scene name='initialview01'>2hky</scene>
| + | <StructureSection load='2hky' size='340' side='right'caption='[[2hky]]' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[2hky]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HKY FirstGlance]. <br> |
| - | |ACTIVITY= | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 15 models</td></tr> |
| - | |GENE= RNASE7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hky OCA], [https://pdbe.org/2hky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hky RCSB], [https://www.ebi.ac.uk/pdbsum/2hky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hky ProSAT]</span></td></tr> |
| - | }}
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RNAS7_HUMAN RNAS7_HUMAN] Exhibits a potent RNase activity. Has broad-spectrum antimicrobial activity against many pathogenic microorganisms and remarkably potent activity (lethal dose of 90% < 30 nM) against a vancomycin resistant Enterococcus faecium.<ref>PMID:12244054</ref> <ref>PMID:12527768</ref> <ref>PMID:17150966</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hk/2hky_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hky ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The ubiquitous ribonucleases (RNases) play important roles in RNA metabolism, angiogenesis, neurotoxicity, and antitumor or antimicrobial activity. Only the antimicrobial RNases possess high positively charged residues, although their mechanisms of action remain unclear. Here, we report on the role of cationic residues of human RNase7 (hRNase7) in its antimicrobial activity. It exerted antimicrobial activity against bacteria and yeast, even at 4 degrees C. The bacterial membrane became permeable to the DNA-binding dye SYTOX(R) Green in only a few minutes after bactericidal RNase treatment. NMR studies showed that the 22 positively charged residues (Lys(18) and Arg(4)) are distributed into three clusters on the surface of hRNase7. The first cluster, K(1),K(3),K(111),K(112), was located at the flexible coil near the N terminus, whereas the other two, K(32),K(35) and K(96),R(97),K(100), were located on rigid secondary structures. Mutagenesis studies showed that the flexible cluster K(1),K(3),K(111),K(112), rather than the catalytic residues His(15), Lys(38), and His(123) or other clusters such as K(32),K(35) and K(96),R(97),K(100), is critical for the bactericidal activity. We suggest that the hRNase7 binds to bacterial membrane and renders the membrane permeable through the flexible and clustered Lys residues K(1),K(3),K(111),K(112). The conformation of hRNase7 can be adapted for pore formation or disruption of bacterial membrane even at 4 degrees C. |
| | | | |
| - | '''NMR solution structure of human RNase 7'''
| + | The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity.,Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:17150966<ref>PMID:17150966</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2hky" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | The ubiquitous ribonucleases (RNases) play important roles in RNA metabolism, angiogenesis, neurotoxicity, and antitumor or antimicrobial activity. Only the antimicrobial RNases possess high positively charged residues, although their mechanisms of action remain unclear. Here, we report on the role of cationic residues of human RNase7 (hRNase7) in its antimicrobial activity. It exerted antimicrobial activity against bacteria and yeast, even at 4 degrees C. The bacterial membrane became permeable to the DNA-binding dye SYTOX(R) Green in only a few minutes after bactericidal RNase treatment. NMR studies showed that the 22 positively charged residues (Lys(18) and Arg(4)) are distributed into three clusters on the surface of hRNase7. The first cluster, K(1),K(3),K(111),K(112), was located at the flexible coil near the N terminus, whereas the other two, K(32),K(35) and K(96),R(97),K(100), were located on rigid secondary structures. Mutagenesis studies showed that the flexible cluster K(1),K(3),K(111),K(112), rather than the catalytic residues His(15), Lys(38), and His(123) or other clusters such as K(32),K(35) and K(96),R(97),K(100), is critical for the bactericidal activity. We suggest that the hRNase7 binds to bacterial membrane and renders the membrane permeable through the flexible and clustered Lys residues K(1),K(3),K(111),K(112). The conformation of hRNase7 can be adapted for pore formation or disruption of bacterial membrane even at 4 degrees C.
| + | *[[Ribonuclease 3D structures|Ribonuclease 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 2HKY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HKY OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity., Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD, J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17150966 17150966]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, C.]] | + | [[Category: Chen C]] |
| - | [[Category: Huang, Y C.]] | + | [[Category: Huang Y-C]] |
| - | [[Category: Lou, Y C.]] | + | [[Category: Lou Y-C]] |
| - | [[Category: antimicrobial activity]]
| + | |
| - | [[Category: rnase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:18:26 2008''
| + | |
| Structural highlights
Function
RNAS7_HUMAN Exhibits a potent RNase activity. Has broad-spectrum antimicrobial activity against many pathogenic microorganisms and remarkably potent activity (lethal dose of 90% < 30 nM) against a vancomycin resistant Enterococcus faecium.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The ubiquitous ribonucleases (RNases) play important roles in RNA metabolism, angiogenesis, neurotoxicity, and antitumor or antimicrobial activity. Only the antimicrobial RNases possess high positively charged residues, although their mechanisms of action remain unclear. Here, we report on the role of cationic residues of human RNase7 (hRNase7) in its antimicrobial activity. It exerted antimicrobial activity against bacteria and yeast, even at 4 degrees C. The bacterial membrane became permeable to the DNA-binding dye SYTOX(R) Green in only a few minutes after bactericidal RNase treatment. NMR studies showed that the 22 positively charged residues (Lys(18) and Arg(4)) are distributed into three clusters on the surface of hRNase7. The first cluster, K(1),K(3),K(111),K(112), was located at the flexible coil near the N terminus, whereas the other two, K(32),K(35) and K(96),R(97),K(100), were located on rigid secondary structures. Mutagenesis studies showed that the flexible cluster K(1),K(3),K(111),K(112), rather than the catalytic residues His(15), Lys(38), and His(123) or other clusters such as K(32),K(35) and K(96),R(97),K(100), is critical for the bactericidal activity. We suggest that the hRNase7 binds to bacterial membrane and renders the membrane permeable through the flexible and clustered Lys residues K(1),K(3),K(111),K(112). The conformation of hRNase7 can be adapted for pore formation or disruption of bacterial membrane even at 4 degrees C.
The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity.,Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:17150966[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Harder J, Schroder JM. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem. 2002 Nov 29;277(48):46779-84. Epub 2002 Sep 18. PMID:12244054 doi:http://dx.doi.org/10.1074/jbc.M207587200
- ↑ Zhang J, Dyer KD, Rosenberg HF. Human RNase 7: a new cationic ribonuclease of the RNase A superfamily. Nucleic Acids Res. 2003 Jan 15;31(2):602-7. PMID:12527768
- ↑ Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD. The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity. J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:17150966 doi:10.1074/jbc.M607321200
- ↑ Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD. The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity. J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:17150966 doi:10.1074/jbc.M607321200
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