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- | {{Seed}} | |
- | [[Image:2pms.png|left|200px]] | |
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- | <!--
| + | ==Crystal structure of the complex of human lactoferrin N-lobe and lactoferrin-binding domain of pneumococcal surface protein A== |
- | The line below this paragraph, containing "STRUCTURE_2pms", creates the "Structure Box" on the page.
| + | <StructureSection load='2pms' size='340' side='right'caption='[[2pms]], [[Resolution|resolution]] 2.91Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2pms]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PMS FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.91Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | {{STRUCTURE_2pms| PDB=2pms | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pms OCA], [https://pdbe.org/2pms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pms RCSB], [https://www.ebi.ac.uk/pdbsum/2pms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pms ProSAT]</span></td></tr> |
| + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/TRFL_HUMAN TRFL_HUMAN] Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref> Lactotransferrin has antimicrobial activity which depends on the extracellular cation concentration.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref> Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref> The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity.<ref>PMID:12535064</ref> <ref>PMID:22320386</ref> Isoform DeltaLf: transcription factor with antiproliferative properties and inducing cell cycle arrest. Binds to DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters.<ref>PMID:12535064</ref> <ref>PMID:22320386</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/pm/2pms_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=2pms ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | Human lactoferrin, a component of the innate immune system, kills a wide variety of microorganisms including the Gram positive bacteria Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) efficiently inhibits this bactericidal action. The crystal structure of a complex of the lactoferrin-binding domain of PspA with the N-lobe of human lactoferrin reveals direct and specific interactions between the negatively charged surface of PspA helices and the highly cationic lactoferricin moiety of lactoferrin. Binding of PspA blocks surface accessibility of this bactericidal peptide preventing it from penetrating the bacterial membrane. Results of site-directed mutagenesis, in vitro protein binding assays and isothermal titration calorimetry measurements corroborate that the specific electrostatic interactions observed in the crystal structure represent major associations between PspA and lactoferrin. The structure provides a snapshot of the protective mechanism utilized by pathogens against the host's first line of defense. PspA represents a major virulence factor and a promising vaccine candidate. Insights from the structure of the complex have implications for designing therapeutic strategies for treatment and prevention of pneumococcal diseases that remain a major public health problem worldwide. |
| | | |
- | ===Crystal structure of the complex of human lactoferrin N-lobe and lactoferrin-binding domain of pneumococcal surface protein A===
| + | Structure of a complex of human lactoferrin N-lobe with pneumococcal surface protein a provides insight into microbial defense mechanism.,Senkovich O, Cook WJ, Mirza S, Hollingshead SK, Protasevich II, Briles DE, Chattopadhyay D J Mol Biol. 2007 Jul 20;370(4):701-13. Epub 2007 May 10. PMID:17543335<ref>PMID:17543335</ref> |
| | | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> |
| + | <div class="pdbe-citations 2pms" style="background-color:#fffaf0;"></div> |
| | | |
- | <!--
| + | ==See Also== |
- | The line below this paragraph, {{ABSTRACT_PUBMED_17543335}}, adds the Publication Abstract to the page
| + | *[[Lactoferrin|Lactoferrin]] |
- | (as it appears on PubMed at http://www.pubmed.gov), where 17543335 is the PubMed ID number.
| + | == References == |
- | -->
| + | <references/> |
- | {{ABSTRACT_PUBMED_17543335}}
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | |
- | 2PMS is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PMS OCA].
| + | |
- | | + | |
- | ==Reference== | + | |
- | Structure of a complex of human lactoferrin N-lobe with pneumococcal surface protein a provides insight into microbial defense mechanism., Senkovich O, Cook WJ, Mirza S, Hollingshead SK, Protasevich II, Briles DE, Chattopadhyay D, J Mol Biol. 2007 Jul 20;370(4):701-13. Epub 2007 May 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17543335 17543335]
| + | |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
| [[Category: Streptococcus pneumoniae]] | | [[Category: Streptococcus pneumoniae]] |
- | [[Category: Chattopadhyay, D.]] | + | [[Category: Chattopadhyay D]] |
- | [[Category: Cook, W J.]] | + | [[Category: Cook WJ]] |
- | [[Category: Senkovich, O.]] | + | [[Category: Senkovich O]] |
- | [[Category: Lactoferrin]]
| + | |
- | [[Category: Pneumococcal surface protein some]]
| + | |
- | [[Category: Protein-protein complex]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:52:42 2008''
| + | |
| Structural highlights
2pms is a 4 chain structure with sequence from Homo sapiens and Streptococcus pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Method: | X-ray diffraction, Resolution 2.91Å |
Ligands: | , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TRFL_HUMAN Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.[1] [2] Lactotransferrin has antimicrobial activity which depends on the extracellular cation concentration.[3] [4] Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.[5] [6] The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity.[7] [8] Isoform DeltaLf: transcription factor with antiproliferative properties and inducing cell cycle arrest. Binds to DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters.[9] [10]
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
Human lactoferrin, a component of the innate immune system, kills a wide variety of microorganisms including the Gram positive bacteria Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) efficiently inhibits this bactericidal action. The crystal structure of a complex of the lactoferrin-binding domain of PspA with the N-lobe of human lactoferrin reveals direct and specific interactions between the negatively charged surface of PspA helices and the highly cationic lactoferricin moiety of lactoferrin. Binding of PspA blocks surface accessibility of this bactericidal peptide preventing it from penetrating the bacterial membrane. Results of site-directed mutagenesis, in vitro protein binding assays and isothermal titration calorimetry measurements corroborate that the specific electrostatic interactions observed in the crystal structure represent major associations between PspA and lactoferrin. The structure provides a snapshot of the protective mechanism utilized by pathogens against the host's first line of defense. PspA represents a major virulence factor and a promising vaccine candidate. Insights from the structure of the complex have implications for designing therapeutic strategies for treatment and prevention of pneumococcal diseases that remain a major public health problem worldwide.
Structure of a complex of human lactoferrin N-lobe with pneumococcal surface protein a provides insight into microbial defense mechanism.,Senkovich O, Cook WJ, Mirza S, Hollingshead SK, Protasevich II, Briles DE, Chattopadhyay D J Mol Biol. 2007 Jul 20;370(4):701-13. Epub 2007 May 10. PMID:17543335[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Hendrixson DR, Qiu J, Shewry SC, Fink DL, Petty S, Baker EN, Plaut AG, St Geme JW 3rd. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Mol Microbiol. 2003 Feb;47(3):607-17. PMID:12535064
- ↑ Mariller C, Hardiville S, Hoedt E, Huvent I, Pina-Canseco S, Pierce A. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012 Jun;90(3):307-19. doi: 10.1139/o11-070. Epub 2012 Feb 9. PMID:22320386 doi:http://dx.doi.org/10.1139/o11-070
- ↑ Senkovich O, Cook WJ, Mirza S, Hollingshead SK, Protasevich II, Briles DE, Chattopadhyay D. Structure of a complex of human lactoferrin N-lobe with pneumococcal surface protein a provides insight into microbial defense mechanism. J Mol Biol. 2007 Jul 20;370(4):701-13. Epub 2007 May 10. PMID:17543335 doi:10.1016/j.jmb.2007.04.075
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