2aps: Difference between revisions
New page: left|200px<br /><applet load="2aps" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aps, resolution 1.9Å" /> '''CU/ZN SUPEROXIDE DISM... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2aps.gif|left|200px]]<br /><applet load="2aps" size=" | [[Image:2aps.gif|left|200px]]<br /><applet load="2aps" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2aps, resolution 1.9Å" /> | caption="2aps, resolution 1.9Å" /> | ||
'''CU/ZN SUPEROXIDE DISMUTASE FROM ACTINOBACILLUS PLEUROPNEUMONIAE'''<br /> | '''CU/ZN SUPEROXIDE DISMUTASE FROM ACTINOBACILLUS PLEUROPNEUMONIAE'''<br /> | ||
==Overview== | ==Overview== | ||
Macrophages and neutrophils protect animals from microbial infection in | Macrophages and neutrophils protect animals from microbial infection in part by issuing a burst of toxic superoxide radicals when challenged. To counteract this onslaught, many Gram-negative bacterial pathogens possess periplasmic Cu,Zn superoxide dismutases (SODs), which act on superoxide to yield molecular oxygen and hydrogen peroxide. We have solved the X-ray crystal structure of the Cu,Zn SOD from Actinobacillus pleuropneumoniae, a major porcine pathogen, by molecular replacement at 1.9 A resolution. The structure reveals that the dimeric bacterial enzymes form a structurally homologous class defined by a water-mediated dimer interface, and share with all Cu,Zn SODs the Greek-key beta-barrel subunit fold with copper and zinc ions located at the base of a deep loop-enclosed active-site channel. Our structure-based sequence alignment of the bacterial enzymes explains the monomeric nature of at least two of these, and suggests that there may be at least one additional structural class for the bacterial SODs. Two metal-mediated crystal contacts yielded our C222(1) crystals, and the geometry of these sites could be engineered into proteins recalcitrant to crystallization in their native form. This work highlights structural differences between eukaryotic and prokaryotic Cu,Zn SODs, as well as similarities and differences among prokaryotic SODs, and lays the groundwork for development of antimicrobial drugs that specifically target periplasmic Cu,Zn SODs of bacterial pathogens. | ||
==About this Structure== | ==About this Structure== | ||
2APS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Actinobacillus_pleuropneumoniae Actinobacillus pleuropneumoniae] with CU and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2APS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Actinobacillus_pleuropneumoniae Actinobacillus pleuropneumoniae] with <scene name='pdbligand=CU:'>CU</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2APS OCA]. | ||
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Actinobacillus pleuropneumoniae]] | [[Category: Actinobacillus pleuropneumoniae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Forest, K | [[Category: Forest, K T.]] | ||
[[Category: Getzoff, E | [[Category: Getzoff, E D.]] | ||
[[Category: Kroll, J | [[Category: Kroll, J S.]] | ||
[[Category: Langford, P | [[Category: Langford, P R.]] | ||
[[Category: CU]] | [[Category: CU]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
| Line 24: | Line 24: | ||
[[Category: water-mediated dimer]] | [[Category: water-mediated dimer]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:29:38 2008'' | ||
Revision as of 17:29, 21 February 2008
|
CU/ZN SUPEROXIDE DISMUTASE FROM ACTINOBACILLUS PLEUROPNEUMONIAE
OverviewOverview
Macrophages and neutrophils protect animals from microbial infection in part by issuing a burst of toxic superoxide radicals when challenged. To counteract this onslaught, many Gram-negative bacterial pathogens possess periplasmic Cu,Zn superoxide dismutases (SODs), which act on superoxide to yield molecular oxygen and hydrogen peroxide. We have solved the X-ray crystal structure of the Cu,Zn SOD from Actinobacillus pleuropneumoniae, a major porcine pathogen, by molecular replacement at 1.9 A resolution. The structure reveals that the dimeric bacterial enzymes form a structurally homologous class defined by a water-mediated dimer interface, and share with all Cu,Zn SODs the Greek-key beta-barrel subunit fold with copper and zinc ions located at the base of a deep loop-enclosed active-site channel. Our structure-based sequence alignment of the bacterial enzymes explains the monomeric nature of at least two of these, and suggests that there may be at least one additional structural class for the bacterial SODs. Two metal-mediated crystal contacts yielded our C222(1) crystals, and the geometry of these sites could be engineered into proteins recalcitrant to crystallization in their native form. This work highlights structural differences between eukaryotic and prokaryotic Cu,Zn SODs, as well as similarities and differences among prokaryotic SODs, and lays the groundwork for development of antimicrobial drugs that specifically target periplasmic Cu,Zn SODs of bacterial pathogens.
About this StructureAbout this Structure
2APS is a Single protein structure of sequence from Actinobacillus pleuropneumoniae with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Cu,Zn superoxide dismutase structure from a microbial pathogen establishes a class with a conserved dimer interface., Forest KT, Langford PR, Kroll JS, Getzoff ED, J Mol Biol. 2000 Feb 11;296(1):145-53. PMID:10656823
Page seeded by OCA on Thu Feb 21 16:29:38 2008