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| - | [[Image:1s1m.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1s1m| PDB=1s1m | SCENE= }} | | {{STRUCTURE_1s1m| PDB=1s1m | SCENE= }} |
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| - | '''Crystal Structure of E. Coli CTP Synthetase'''
| + | ===Crystal Structure of E. Coli CTP Synthetase=== |
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| - | ==Overview==
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| - | Cytidine triphosphate synthetases (CTPSs) produce CTP from UTP and glutamine, and regulate intracellular CTP levels through interactions with the four ribonucleotide triphosphates. We solved the 2.3-A resolution crystal structure of Escherichia coli CTPS using Hg-MAD phasing. The structure reveals a nearly symmetric 222 tetramer, in which each bifunctional monomer contains a dethiobiotin synthetase-like amidoligase N-terminal domain and a Type 1 glutamine amidotransferase C-terminal domain. For each amidoligase active site, essential ATP- and UTP-binding surfaces are contributed by three monomers, suggesting that activity requires tetramer formation, and that a nucleotide-dependent dimer-tetramer equilibrium contributes to the observed positive cooperativity. A gated channel that spans 25 A between the glutamine hydrolysis and amidoligase active sites provides a path for ammonia diffusion. The channel is accessible to solvent at the base of a cleft adjoining the glutamine hydrolysis active site, providing an entry point for exogenous ammonia. Guanine nucleotide binding sites of structurally related GTPases superimpose on this cleft, providing insights into allosteric regulation by GTP. Mutations that confer nucleoside drug resistance and release CTP inhibition map to a pocket that neighbors the UTP-binding site and can accommodate a pyrimidine ring. Its location suggests that competitive feedback inhibition is affected via a distinct product/drug binding site that overlaps the substrate triphosphate binding site. Overall, the E. coli structure provides a framework for homology modeling of other CTPSs and structure-based design of anti-CTPS therapeutics.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15157079}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15157079 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15157079}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ctp synthetase]] | | [[Category: Ctp synthetase]] |
| | [[Category: Cytidine 5'-triphosphate synthase]] | | [[Category: Cytidine 5'-triphosphate synthase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:11:07 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:25:26 2008'' |
Revision as of 11:25, 28 July 2008
Template:STRUCTURE 1s1m
Crystal Structure of E. Coli CTP Synthetase
Template:ABSTRACT PUBMED 15157079
About this Structure
1S1M is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Crystal structure of Escherichia coli cytidine triphosphate synthetase, a nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets., Endrizzi JA, Kim H, Anderson PM, Baldwin EP, Biochemistry. 2004 Jun 1;43(21):6447-63. PMID:15157079
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