1q3t
From Proteopedia
(New page: 200px<br /><applet load="1q3t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q3t" /> '''Solution structure and function of an essent...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1q3t.gif|left|200px]]<br /><applet load="1q3t" size=" | + | [[Image:1q3t.gif|left|200px]]<br /><applet load="1q3t" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1q3t" /> | caption="1q3t" /> | ||
'''Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae'''<br /> | '''Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Streptococcus pneumoniae is a major human pathogen that causes high | + | Streptococcus pneumoniae is a major human pathogen that causes high mortality and morbidity and has developed resistance to many antibiotics. We show that the gene product from SP1603, identified from S. pneumoniae TIGR4, is a CMP kinase that is essential for bacterial growth. It represents an attractive drug target for the development of a novel antibiotic to overcome the problems of drug resistance development for this organism. Here we describe the three-dimensional solution structure of the S. pneumoniae CMP kinase as determined by NMR spectroscopy. The structure consists of eight alpha-helices and two beta-sheets that fold into the classical core domain, the substrate-binding domain, and the LID domain. The three domains of the protein pack together to form a central cavity for substrate-binding and enzymatic catalysis. The S. pneumoniae CMP kinase resembles the fold of the Escherichia coli homolog. An insertion of one residue is observed at the beta-turn in the substrate-binding domain of the S. pneumoniae CMP kinase when compared with the E. coli homolog. Chemical shift perturbations caused by the binding of CMP, CDP, and ATP revealed that CMP or CDP binds to the junction between the core and substrate-binding domains, whereas ATP binds to the junction between the core and LID domains. From NMR relaxation studies, we determined that the loops in the LID domain are highly mobile. These mobile loops could aid in the closing/opening of the LID domain during enzyme catalysis. |
==About this Structure== | ==About this Structure== | ||
| - | 1Q3T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Active as [http://en.wikipedia.org/wiki/Cytidylate_kinase Cytidylate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.14 2.7.4.14] Full crystallographic information is available from [http:// | + | 1Q3T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Active as [http://en.wikipedia.org/wiki/Cytidylate_kinase Cytidylate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.14 2.7.4.14] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q3T OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptococcus pneumoniae]] | [[Category: Streptococcus pneumoniae]] | ||
| - | [[Category: Hajduk, P | + | [[Category: Hajduk, P J.]] |
| - | [[Category: Kakavas, S | + | [[Category: Kakavas, S J.]] |
| - | [[Category: Lerner, C | + | [[Category: Lerner, C G.]] |
[[Category: Mack, J.]] | [[Category: Mack, J.]] | ||
| - | [[Category: Olejniczak, E | + | [[Category: Olejniczak, E T.]] |
| - | [[Category: Saiki, A | + | [[Category: Saiki, A Y.]] |
[[Category: Yu, L.]] | [[Category: Yu, L.]] | ||
[[Category: cmp kinase]] | [[Category: cmp kinase]] | ||
| Line 25: | Line 25: | ||
[[Category: nucleotide monophosphate kinase]] | [[Category: nucleotide monophosphate kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:35:36 2008'' |
Revision as of 12:35, 21 February 2008
|
Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae
Overview
Streptococcus pneumoniae is a major human pathogen that causes high mortality and morbidity and has developed resistance to many antibiotics. We show that the gene product from SP1603, identified from S. pneumoniae TIGR4, is a CMP kinase that is essential for bacterial growth. It represents an attractive drug target for the development of a novel antibiotic to overcome the problems of drug resistance development for this organism. Here we describe the three-dimensional solution structure of the S. pneumoniae CMP kinase as determined by NMR spectroscopy. The structure consists of eight alpha-helices and two beta-sheets that fold into the classical core domain, the substrate-binding domain, and the LID domain. The three domains of the protein pack together to form a central cavity for substrate-binding and enzymatic catalysis. The S. pneumoniae CMP kinase resembles the fold of the Escherichia coli homolog. An insertion of one residue is observed at the beta-turn in the substrate-binding domain of the S. pneumoniae CMP kinase when compared with the E. coli homolog. Chemical shift perturbations caused by the binding of CMP, CDP, and ATP revealed that CMP or CDP binds to the junction between the core and substrate-binding domains, whereas ATP binds to the junction between the core and LID domains. From NMR relaxation studies, we determined that the loops in the LID domain are highly mobile. These mobile loops could aid in the closing/opening of the LID domain during enzyme catalysis.
About this Structure
1Q3T is a Single protein structure of sequence from Streptococcus pneumoniae. Active as Cytidylate kinase, with EC number 2.7.4.14 Full crystallographic information is available from OCA.
Reference
Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae., Yu L, Mack J, Hajduk PJ, Kakavas SJ, Saiki AY, Lerner CG, Olejniczak ET, Protein Sci. 2003 Nov;12(11):2613-21. PMID:14573872
Page seeded by OCA on Thu Feb 21 14:35:36 2008
