1bsk: Difference between revisions
New page: left|200px<br /><applet load="1bsk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bsk, resolution 3.0Å" /> '''ZINC DEFORMYLASE INHI... |
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[[Image:1bsk.gif|left|200px]]<br /><applet load="1bsk" size=" | [[Image:1bsk.gif|left|200px]]<br /><applet load="1bsk" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1bsk, resolution 3.0Å" /> | caption="1bsk, resolution 3.0Å" /> | ||
'''ZINC DEFORMYLASE INHIBITOR COMPLEX FROM E.COLI'''<br /> | '''ZINC DEFORMYLASE INHIBITOR COMPLEX FROM E.COLI'''<br /> | ||
==Overview== | ==Overview== | ||
While protein synthesis in bacteria begins with a formylated methionine, the formyl group of the nascent polypeptide is removed by peptide | While protein synthesis in bacteria begins with a formylated methionine, the formyl group of the nascent polypeptide is removed by peptide deformylase. Since eukaryotic protein synthesis does not involve formylation and deformylation at the N-terminus, there has been increasing interest in peptide deformylase as a potential target for antibacterial chemotherapy. Toward this end and to aid in the design of effective antibiotics targeting peptide deformylase, the structures of the protein-inhibitor complexes of both the cobalt and the zinc containing Escherichia coli peptide deformylase bound to the transition-state analogue, (S)-2-O-(H-phosphonoxy)-L-caproyl-L-leucyl-p-nitroanilide (PCLNA), have been determined. The proteins for both deformylase-inhibitor complexes show basically the same fold as for the native enzyme. The PCLNA inhibitor adopts an extended conformation and fits nicely into a hydrophobic cavity located near the metal site. On the basis of these structures, guidelines for the design of high-affinity deformylase inhibitors are suggested. As our results show that the protein residues which interact with the PCLNA inhibitor are conserved over a wide variety of species, we suggest that antibiotics targeting deformylase could have wide applicability. | ||
==About this Structure== | ==About this Structure== | ||
1BSK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ZN, PO4 and MLN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N-formylmethionylaminoacyl-tRNA_deformylase N-formylmethionylaminoacyl-tRNA deformylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.27 3.5.1.27] Full crystallographic information is available from [http:// | 1BSK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=MLN:'>MLN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N-formylmethionylaminoacyl-tRNA_deformylase N-formylmethionylaminoacyl-tRNA deformylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.27 3.5.1.27] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BSK OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: N-formylmethionylaminoacyl-tRNA deformylase]] | [[Category: N-formylmethionylaminoacyl-tRNA deformylase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chan, M | [[Category: Chan, M K.]] | ||
[[Category: Gong, W.]] | [[Category: Gong, W.]] | ||
[[Category: Hao, B.]] | [[Category: Hao, B.]] | ||
[[Category: Hu, Y.]] | [[Category: Hu, Y.]] | ||
[[Category: Pei, D.]] | [[Category: Pei, D.]] | ||
[[Category: Rajagopalan, P | [[Category: Rajagopalan, P T.]] | ||
[[Category: MLN]] | [[Category: MLN]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
| Line 27: | Line 27: | ||
[[Category: metalloproteinase]] | [[Category: metalloproteinase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:58:48 2008'' | ||
Revision as of 12:58, 21 February 2008
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ZINC DEFORMYLASE INHIBITOR COMPLEX FROM E.COLI
OverviewOverview
While protein synthesis in bacteria begins with a formylated methionine, the formyl group of the nascent polypeptide is removed by peptide deformylase. Since eukaryotic protein synthesis does not involve formylation and deformylation at the N-terminus, there has been increasing interest in peptide deformylase as a potential target for antibacterial chemotherapy. Toward this end and to aid in the design of effective antibiotics targeting peptide deformylase, the structures of the protein-inhibitor complexes of both the cobalt and the zinc containing Escherichia coli peptide deformylase bound to the transition-state analogue, (S)-2-O-(H-phosphonoxy)-L-caproyl-L-leucyl-p-nitroanilide (PCLNA), have been determined. The proteins for both deformylase-inhibitor complexes show basically the same fold as for the native enzyme. The PCLNA inhibitor adopts an extended conformation and fits nicely into a hydrophobic cavity located near the metal site. On the basis of these structures, guidelines for the design of high-affinity deformylase inhibitors are suggested. As our results show that the protein residues which interact with the PCLNA inhibitor are conserved over a wide variety of species, we suggest that antibiotics targeting deformylase could have wide applicability.
About this StructureAbout this Structure
1BSK is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as N-formylmethionylaminoacyl-tRNA deformylase, with EC number 3.5.1.27 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the design of antibiotics targeting peptide deformylase., Hao B, Gong W, Rajagopalan PT, Zhou Y, Pei D, Chan MK, Biochemistry. 1999 Apr 13;38(15):4712-9. PMID:10200158
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