2pm4: Difference between revisions
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[[Image:2pm4.jpg|left|200px]] | [[Image:2pm4.jpg|left|200px]] | ||
'''Human alpha-defensin 1 (multiple Arg->Lys mutant)''' | {{Structure | ||
|PDB= 2pm4 |SIZE=350|CAPTION= <scene name='initialview01'>2pm4</scene>, resolution 1.95Å | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= | |||
|GENE= DEFA1, DEF1, DEFA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Human alpha-defensin 1 (multiple Arg->Lys mutant)''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2PM4 is a [ | 2PM4 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=2PM4 OCA]. | ||
==Reference== | ==Reference== | ||
Toward understanding the cationicity of defensins. Arg and Lys versus their noncoded analogs., Zou G, de Leeuw E, Li C, Pazgier M, Li C, Zeng P, Lu WY, Lubkowski J, Lu W, J Biol Chem. 2007 Jul 6;282(27):19653-65. Epub 2007 Apr 23. PMID:[http:// | Toward understanding the cationicity of defensins. Arg and Lys versus their noncoded analogs., Zou G, de Leeuw E, Li C, Pazgier M, Li C, Zeng P, Lu WY, Lubkowski J, Lu W, J Biol Chem. 2007 Jul 6;282(27):19653-65. Epub 2007 Apr 23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17452329 17452329] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: mutant]] | [[Category: mutant]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:14:45 2008'' | ||
Revision as of 19:14, 20 March 2008
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| , resolution 1.95Å | |||||||
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| Gene: | DEFA1, DEF1, DEFA2 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human alpha-defensin 1 (multiple Arg->Lys mutant)
OverviewOverview
Human defensins are a family of small antimicrobial proteins found predominantly in leukocytes and epithelial cells that play important roles in the innate and adaptive immune defense against microbial infection. The most distinct molecular feature of defensins is cationicity, manifested by abundant Arg and/or Lys residues in their sequences. Sequence analysis indicates that Arg is strongly selected over Lys in alpha-defensins but not in beta-defensins. To understand this Arg/Lys disparity in defensins, we chemically synthesized human alpha-defensin 1 (HNP1) and several HNP1 analogs where three Arg residues were replaced by each of the following six alpha-amino acids: Lys, ornithine (Orn), diaminobutyric acid (Dab), diaminopropionic acid (Dap), N,N-dimethyl-Lys ((diMe)Lys), and homo-Arg ((homo)Arg). In addition, we prepared human beta-defensin 1 (hBD1) and (Lys-->Arg)hBD1 in which all four Lys residues were substituted for Arg. Bactericidal activity assays revealed the following. 1) Arg-containing HNP1 and (Lys-->Arg)hBD1 are functionally better than Lys-HNP1 and hBD1, respectively; the difference between Arg and Lys is more evident in the alpha-defensin than in the beta-defensin and is more evident at low salt concentrations than at high salt concentrations. 2) For HNP1, the Arg/Lys disparity is much more pronounced with Staphylococcus aureus than with Escherichia coli, and the Arg-rich HNP1 kills bacteria faster than its Lys-rich analog. 3) Arg and Lys appear to have optimal chain lengths for bacterial killing as shortening Lys or lengthening Arg in HNP1 invariably becomes functionally deleterious. Our findings provide insights into the Arg/Lys disparity in defensins, and shed light on the cationicity of defensins with respect to their antimicrobial activity and specificity.
DiseaseDisease
Known disease associated with this structure: Mental retardation, X-linked, South African type OMIM:[300243]
About this StructureAbout this Structure
2PM4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Toward understanding the cationicity of defensins. Arg and Lys versus their noncoded analogs., Zou G, de Leeuw E, Li C, Pazgier M, Li C, Zeng P, Lu WY, Lubkowski J, Lu W, J Biol Chem. 2007 Jul 6;282(27):19653-65. Epub 2007 Apr 23. PMID:17452329
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