1kny
From Proteopedia
(New page: 200px<br /><applet load="1kny" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kny, resolution 2.5Å" /> '''KANAMYCIN NUCLEOTIDYL...) |
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| - | [[Image:1kny.gif|left|200px]]<br /><applet load="1kny" size=" | + | [[Image:1kny.gif|left|200px]]<br /><applet load="1kny" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1kny, resolution 2.5Å" /> | caption="1kny, resolution 2.5Å" /> | ||
'''KANAMYCIN NUCLEOTIDYLTRANSFERASE'''<br /> | '''KANAMYCIN NUCLEOTIDYLTRANSFERASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Kanamycin nucleotidyltransferase (KNTase) is a plasmid-coded enzyme | + | Kanamycin nucleotidyltransferase (KNTase) is a plasmid-coded enzyme responsible for some types of bacterial resistance to aminoglycosides. The enzyme deactivates various antibiotics by transferring a nucleoside monophosphate group from ATP to the 4'-hydroxyl group of the drug. Detailed knowledge of the interactions between the protein and the substrates may lead to the design of aminoglycosides less susceptible to bacterial deactivation. Here we describe the structure of KNTase complexed with both the nonhydrolyzable nucleotide analog AMPCPP and kanamycin. Crystals employed in the investigation were grown from poly(ethylene glycol) solutions and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 57.3 A, b = 102.2 A, c = 101.8 A, and one dimer in the asymmetric unit. Least-squares refinement of the model at 2.5 A resolution reduced the crystallographic R factor to 16.8%. The binding pockets for both the nucleotide and the antibiotic are extensively exposed to the solvent and are composed of amino acid residues contributed by both subunits in the dimer. There are few specific interactions between the protein and the adenine ring of the nucleotide; rather the AMPCPP molecule is locked into position by extensive hydrogen bonding between the alpha-, beta-, and gamma-phosphates and protein side chains. This, in part, may explain the observation that the enzyme can utilize other nucleotides such as GTP and UTP. The 4'-hydroxyl group of the antibiotic is approximately 5 A from the alpha-phosphorus of the nucleotide and is in the proper orientation for a single in-line displacement attack at the phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS) |
==About this Structure== | ==About this Structure== | ||
| - | 1KNY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with MG, APC and KAN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1KNY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=APC:'>APC</scene> and <scene name='pdbligand=KAN:'>KAN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KNY OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: Benning, M | + | [[Category: Benning, M M.]] |
| - | [[Category: Holden, H | + | [[Category: Holden, H M.]] |
| - | [[Category: Pedersen, L | + | [[Category: Pedersen, L C.]] |
[[Category: APC]] | [[Category: APC]] | ||
[[Category: KAN]] | [[Category: KAN]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:36:08 2008'' |
Revision as of 11:36, 21 February 2008
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KANAMYCIN NUCLEOTIDYLTRANSFERASE
Overview
Kanamycin nucleotidyltransferase (KNTase) is a plasmid-coded enzyme responsible for some types of bacterial resistance to aminoglycosides. The enzyme deactivates various antibiotics by transferring a nucleoside monophosphate group from ATP to the 4'-hydroxyl group of the drug. Detailed knowledge of the interactions between the protein and the substrates may lead to the design of aminoglycosides less susceptible to bacterial deactivation. Here we describe the structure of KNTase complexed with both the nonhydrolyzable nucleotide analog AMPCPP and kanamycin. Crystals employed in the investigation were grown from poly(ethylene glycol) solutions and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 57.3 A, b = 102.2 A, c = 101.8 A, and one dimer in the asymmetric unit. Least-squares refinement of the model at 2.5 A resolution reduced the crystallographic R factor to 16.8%. The binding pockets for both the nucleotide and the antibiotic are extensively exposed to the solvent and are composed of amino acid residues contributed by both subunits in the dimer. There are few specific interactions between the protein and the adenine ring of the nucleotide; rather the AMPCPP molecule is locked into position by extensive hydrogen bonding between the alpha-, beta-, and gamma-phosphates and protein side chains. This, in part, may explain the observation that the enzyme can utilize other nucleotides such as GTP and UTP. The 4'-hydroxyl group of the antibiotic is approximately 5 A from the alpha-phosphorus of the nucleotide and is in the proper orientation for a single in-line displacement attack at the phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)
About this Structure
1KNY is a Single protein structure of sequence from Staphylococcus aureus with , and as ligands. Full crystallographic information is available from OCA.
Reference
Structural investigation of the antibiotic and ATP-binding sites in kanamycin nucleotidyltransferase., Pedersen LC, Benning MM, Holden HM, Biochemistry. 1995 Oct 17;34(41):13305-11. PMID:7577914
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