1h7e
From Proteopedia
(New page: 200px<br /><applet load="1h7e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h7e, resolution 1.83Å" /> '''THE STRUCTURE OF CMP...) |
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| - | [[Image:1h7e.gif|left|200px]]<br /><applet load="1h7e" size=" | + | [[Image:1h7e.gif|left|200px]]<br /><applet load="1h7e" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1h7e, resolution 1.83Å" /> | caption="1h7e, resolution 1.83Å" /> | ||
'''THE STRUCTURE OF CMP:2-KETO-3-DEOXY-MANNO-OCTONIC ACID SYNTHETASE AND OF ITS COMPLEXES WITH SUBSTRATES AND SUBSTRATE ANALOGUES, APO-ENZYME'''<br /> | '''THE STRUCTURE OF CMP:2-KETO-3-DEOXY-MANNO-OCTONIC ACID SYNTHETASE AND OF ITS COMPLEXES WITH SUBSTRATES AND SUBSTRATE ANALOGUES, APO-ENZYME'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The enzyme CMP-Kdo synthetase (CKS) catalyzes the activation of the sugar | + | The enzyme CMP-Kdo synthetase (CKS) catalyzes the activation of the sugar Kdo (2-keto-3-deoxy-manno-octonic acid) by forming a monophosphate diester. CKS is a pharmaceutical target because CMP-Kdo is used in the biosynthesis of lipopolysaccharides that are vital for Gram-negative bacteria. We have refined the structure of the unligated capsule-specific CKS from Escherichia coli at 1.8 A resolution (1 A=0.1 nm) and we have established the structures of its complexes with the substrate CTP, with CDP and CMP as well as with the product analog CMP-NeuAc (CMP-sialate) by X-ray diffraction analyses at resolutions between 2.1 A and 2.5 A. The N-terminal domains of the dimeric enzyme bind CTP in a peculiar nucleotide-binding fold, whereas the C-terminal domains form the dimer interface. The observed binding geometries together with the amino acid variabilities during evolution and the locations of a putative Mg(2+) and of a very strongly bound water molecule suggest a pathway for the catalysis. The N-terminal domain shows sequence homology with the CMP-NeuAc synthetases. Moreover, the chain fold and the substrate-binding position of CKS resemble those of other enzymes processing nucleotide-sugars. |
==About this Structure== | ==About this Structure== | ||
| - | 1H7E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Active as [http://en.wikipedia.org/wiki/3-deoxy-manno-octulosonate_cytidylyltransferase 3-deoxy-manno-octulosonate cytidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.38 2.7.7.38] Full crystallographic information is available from [http:// | + | 1H7E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Active as [http://en.wikipedia.org/wiki/3-deoxy-manno-octulosonate_cytidylyltransferase 3-deoxy-manno-octulosonate cytidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.38 2.7.7.38] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H7E OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Jelakovic, S.]] | [[Category: Jelakovic, S.]] | ||
| - | [[Category: Schulz, G | + | [[Category: Schulz, G E.]] |
[[Category: cmp-kdo synthetase]] | [[Category: cmp-kdo synthetase]] | ||
[[Category: lipopolysaccharide biosynthesis]] | [[Category: lipopolysaccharide biosynthesis]] | ||
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[[Category: sugar-activating enzymes]] | [[Category: sugar-activating enzymes]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:18 2008'' |
Revision as of 10:58, 21 February 2008
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THE STRUCTURE OF CMP:2-KETO-3-DEOXY-MANNO-OCTONIC ACID SYNTHETASE AND OF ITS COMPLEXES WITH SUBSTRATES AND SUBSTRATE ANALOGUES, APO-ENZYME
Overview
The enzyme CMP-Kdo synthetase (CKS) catalyzes the activation of the sugar Kdo (2-keto-3-deoxy-manno-octonic acid) by forming a monophosphate diester. CKS is a pharmaceutical target because CMP-Kdo is used in the biosynthesis of lipopolysaccharides that are vital for Gram-negative bacteria. We have refined the structure of the unligated capsule-specific CKS from Escherichia coli at 1.8 A resolution (1 A=0.1 nm) and we have established the structures of its complexes with the substrate CTP, with CDP and CMP as well as with the product analog CMP-NeuAc (CMP-sialate) by X-ray diffraction analyses at resolutions between 2.1 A and 2.5 A. The N-terminal domains of the dimeric enzyme bind CTP in a peculiar nucleotide-binding fold, whereas the C-terminal domains form the dimer interface. The observed binding geometries together with the amino acid variabilities during evolution and the locations of a putative Mg(2+) and of a very strongly bound water molecule suggest a pathway for the catalysis. The N-terminal domain shows sequence homology with the CMP-NeuAc synthetases. Moreover, the chain fold and the substrate-binding position of CKS resemble those of other enzymes processing nucleotide-sugars.
About this Structure
1H7E is a Single protein structure of sequence from Escherichia coli. Active as 3-deoxy-manno-octulosonate cytidylyltransferase, with EC number 2.7.7.38 Full crystallographic information is available from OCA.
Reference
The structure of CMP:2-keto-3-deoxy-manno-octonic acid synthetase and of its complexes with substrates and substrate analogs., Jelakovic S, Schulz GE, J Mol Biol. 2001 Sep 7;312(1):143-55. PMID:11545592
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