2rhs: Difference between revisions
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'''PheRS from Staphylococcus haemolyticus- rational protein engineering and inhibitor studies''' | '''PheRS from Staphylococcus haemolyticus- rational protein engineering and inhibitor studies''' | ||
==Overview== | |||
In this article, we describe for the first time the high-resolution crystal structure of a phenylalanine tRNA synthetase from the pathogenic bacterium Staphylococcus haemolyticus. We demonstrate the subtle yet important structural differences between this enzyme and the previously described Thermus thermophilus ortholog. We also explain the structure-activity relationship of several recently reported inhibitors. The native enzyme crystals were of poor quality--they only diffracted X-rays to 3-5A resolution. Therefore, we have executed a rational surface mutagenesis strategy that has yielded crystals of this 2300-amino acid multidomain protein, diffracting to 2A or better. This methodology is discussed and contrasted with the more traditional domain truncation approach. | |||
==About this Structure== | ==About this Structure== | ||
2RHS is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Staphylococcus_haemolyticus Staphylococcus haemolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RHS OCA]. | 2RHS is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Staphylococcus_haemolyticus Staphylococcus haemolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RHS OCA]. | ||
==Reference== | |||
Rational protein engineering in action: the first crystal structure of a phenylalanine tRNA synthetase from Staphylococcus haemolyticus., Evdokimov AG, Mekel M, Hutchings K, Narasimhan L, Holler T, McGrath T, Beattie B, Fauman E, Yan C, Heaslet H, Walter R, Finzel B, Ohren J, McConnell P, Braden T, Sun F, Spessard C, Banotai C, Al-Kassim L, Ma W, Wengender P, Kole D, Garceau N, Toogood P, Liu J, J Struct Biol. 2008 Apr;162(1):152-69. Epub 2007 Nov 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18086534 18086534] | |||
[[Category: Phenylalanine--tRNA ligase]] | [[Category: Phenylalanine--tRNA ligase]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Trna]] | [[Category: Trna]] | ||
[[Category: Trna-binding]] | [[Category: Trna-binding]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 7 08:51:26 2008'' | ||
Revision as of 08:51, 7 May 2008
PheRS from Staphylococcus haemolyticus- rational protein engineering and inhibitor studies
OverviewOverview
In this article, we describe for the first time the high-resolution crystal structure of a phenylalanine tRNA synthetase from the pathogenic bacterium Staphylococcus haemolyticus. We demonstrate the subtle yet important structural differences between this enzyme and the previously described Thermus thermophilus ortholog. We also explain the structure-activity relationship of several recently reported inhibitors. The native enzyme crystals were of poor quality--they only diffracted X-rays to 3-5A resolution. Therefore, we have executed a rational surface mutagenesis strategy that has yielded crystals of this 2300-amino acid multidomain protein, diffracting to 2A or better. This methodology is discussed and contrasted with the more traditional domain truncation approach.
About this StructureAbout this Structure
2RHS is a Protein complex structure of sequences from Staphylococcus haemolyticus. Full crystallographic information is available from OCA.
ReferenceReference
Rational protein engineering in action: the first crystal structure of a phenylalanine tRNA synthetase from Staphylococcus haemolyticus., Evdokimov AG, Mekel M, Hutchings K, Narasimhan L, Holler T, McGrath T, Beattie B, Fauman E, Yan C, Heaslet H, Walter R, Finzel B, Ohren J, McConnell P, Braden T, Sun F, Spessard C, Banotai C, Al-Kassim L, Ma W, Wengender P, Kole D, Garceau N, Toogood P, Liu J, J Struct Biol. 2008 Apr;162(1):152-69. Epub 2007 Nov 13. PMID:18086534 Page seeded by OCA on Wed May 7 08:51:26 2008