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New page: left|200px<br /><applet load="1xjf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xjf, resolution 2.40Å" /> '''Structural mechanism...
 
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[[Image:1xjf.gif|left|200px]]<br /><applet load="1xjf" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1xjf.gif|left|200px]]<br /><applet load="1xjf" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1xjf, resolution 2.40&Aring;" />
caption="1xjf, resolution 2.40&Aring;" />
'''Structural mechanism of allosteric substrate specificity in a ribonucleotide reductase: dATP complex'''<br />
'''Structural mechanism of allosteric substrate specificity in a ribonucleotide reductase: dATP complex'''<br />


==Overview==
==Overview==
Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides, into deoxyribonucleotides, which constitute the precursor pools used for, DNA synthesis and repair. Imbalances in these pools increase mutational, rates and are detrimental to the cell. Balanced precursor pools are, maintained primarily through the regulation of the RNR substrate, specificity. Here, the molecular mechanism of the allosteric substrate, specificity regulation is revealed through the structures of a dimeric, coenzyme B12-dependent RNR from Thermotoga maritima, both in complexes, with four effector-substrate nucleotide pairs and in three complexes with, only effector. The mechanism is based on the flexibility of loop 2, a key, structural element, which forms a bridge between the specificity effector, and substrate nucleotides. Substrate specificity is achieved as different, effectors and their cognate substrates stabilize specific discrete loop 2, conformations. The mechanism of substrate specificity regulation is, probably general for most class I and class II RNRs.
Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into deoxyribonucleotides, which constitute the precursor pools used for DNA synthesis and repair. Imbalances in these pools increase mutational rates and are detrimental to the cell. Balanced precursor pools are maintained primarily through the regulation of the RNR substrate specificity. Here, the molecular mechanism of the allosteric substrate specificity regulation is revealed through the structures of a dimeric coenzyme B12-dependent RNR from Thermotoga maritima, both in complexes with four effector-substrate nucleotide pairs and in three complexes with only effector. The mechanism is based on the flexibility of loop 2, a key structural element, which forms a bridge between the specificity effector and substrate nucleotides. Substrate specificity is achieved as different effectors and their cognate substrates stabilize specific discrete loop 2 conformations. The mechanism of substrate specificity regulation is probably general for most class I and class II RNRs.


==About this Structure==
==About this Structure==
1XJF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with MG and DTP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XJF OCA].  
1XJF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=DTP:'>DTP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XJF OCA].  


==Reference==
==Reference==
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[[Category: Eliasson, R.]]
[[Category: Eliasson, R.]]
[[Category: Jordan, A.]]
[[Category: Jordan, A.]]
[[Category: Larsson, K.M.]]
[[Category: Larsson, K M.]]
[[Category: Logan, D.T.]]
[[Category: Logan, D T.]]
[[Category: Nordlund, P.]]
[[Category: Nordlund, P.]]
[[Category: Reichard, P.]]
[[Category: Reichard, P.]]
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[[Category: substrate specificity]]
[[Category: substrate specificity]]


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