1gq9
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The activation of the sugar 2-keto-3-deoxy-manno-octonic acid (Kdo) is, catalyzed by CMP-Kdo synthetase (EC 2.7.7.38) and results in a, monophosphate diester with CMP. The enzyme is a pharmaceutical target, because CMP-Kdo is required for the biosynthesis of lipopolysaccharides, that are vital for Gram-negative bacteria. We have established the, structures of an enzyme complex with the educt CTP and of a complex with, the product CMP-Kdo by X-ray diffraction analyses at 100 K, both at 2.6 A, resolution. The N-terminal domains of the dimeric enzyme bind CTP in a, peculiar nucleotide-binding fold with the beta- and gamma-phosphates, located at the so-called "PP-loop", whereas the C-terminal domains, participate in Kdo binding and in the dimer interface. The unstable, nucleotide-sugar ... | + | The activation of the sugar 2-keto-3-deoxy-manno-octonic acid (Kdo) is, catalyzed by CMP-Kdo synthetase (EC 2.7.7.38) and results in a, monophosphate diester with CMP. The enzyme is a pharmaceutical target, because CMP-Kdo is required for the biosynthesis of lipopolysaccharides, that are vital for Gram-negative bacteria. We have established the, structures of an enzyme complex with the educt CTP and of a complex with, the product CMP-Kdo by X-ray diffraction analyses at 100 K, both at 2.6 A, resolution. The N-terminal domains of the dimeric enzyme bind CTP in a, peculiar nucleotide-binding fold with the beta- and gamma-phosphates, located at the so-called "PP-loop", whereas the C-terminal domains, participate in Kdo binding and in the dimer interface. The unstable, nucleotide-sugar CMP-Kdo was produced in a crystal and stabilized by, freezing to 100 K. Its formation is accompanied by an induced fit, involving mainchain displacements in the 2 A range. The observed binding, conformations together with the amino acid conservation pattern during, evolution and the putative location of the required Mg(2+) ion suggest a, reaction pathway. The enzyme is structurally homologous to the, CMP-N-acetylneuraminic acid synthetases in all parts except for the dimer, interface. Moreover, the chainfold and the substrate-binding positions, resemble those of other enzymes processing nucleotide sugars. |
==About this Structure== | ==About this Structure== | ||
| - | 1GQ9 is a | + | 1GQ9 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 MG and CTP as [http://en.wikipedia.org/wiki/ligands ligands]. 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] Structure known Active Site: CTA. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GQ9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: sugar-activating enzymes]] | [[Category: sugar-activating enzymes]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:32:24 2007'' |
Revision as of 13:27, 5 November 2007
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THE STRUCTURE OF CMP:2-KETO-3-DEOXY-MANNO-OCTONIC ACID SYNTHETASE COMPLEXED WITH CTP AT 100K
Overview
The activation of the sugar 2-keto-3-deoxy-manno-octonic acid (Kdo) is, catalyzed by CMP-Kdo synthetase (EC 2.7.7.38) and results in a, monophosphate diester with CMP. The enzyme is a pharmaceutical target, because CMP-Kdo is required for the biosynthesis of lipopolysaccharides, that are vital for Gram-negative bacteria. We have established the, structures of an enzyme complex with the educt CTP and of a complex with, the product CMP-Kdo by X-ray diffraction analyses at 100 K, both at 2.6 A, resolution. The N-terminal domains of the dimeric enzyme bind CTP in a, peculiar nucleotide-binding fold with the beta- and gamma-phosphates, located at the so-called "PP-loop", whereas the C-terminal domains, participate in Kdo binding and in the dimer interface. The unstable, nucleotide-sugar CMP-Kdo was produced in a crystal and stabilized by, freezing to 100 K. Its formation is accompanied by an induced fit, involving mainchain displacements in the 2 A range. The observed binding, conformations together with the amino acid conservation pattern during, evolution and the putative location of the required Mg(2+) ion suggest a, reaction pathway. The enzyme is structurally homologous to the, CMP-N-acetylneuraminic acid synthetases in all parts except for the dimer, interface. Moreover, the chainfold and the substrate-binding positions, resemble those of other enzymes processing nucleotide sugars.
About this Structure
1GQ9 is a Single protein structure of sequence from Escherichia coli with MG and CTP as ligands. Active as 3-deoxy-manno-octulosonate cytidylyltransferase, with EC number 2.7.7.38 Structure known Active Site: CTA. Full crystallographic information is available from OCA.
Reference
Catalytic mechanism of CMP:2-keto-3-deoxy-manno-octonic acid synthetase as derived from complexes with reaction educt and product., Jelakovic S, Schulz GE, Biochemistry. 2002 Jan 29;41(4):1174-81. PMID:11802716
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