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| {{STRUCTURE_2quh| PDB=2quh | SCENE= }} | | {{STRUCTURE_2quh| PDB=2quh | SCENE= }} |
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| '''Crystal structures of human tryptophanyl-tRNA synthetase in complex with Trp'''
| | ===Crystal structures of human tryptophanyl-tRNA synthetase in complex with Trp=== |
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| ==Overview==
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| Human tryptophanyl-tRNA synthetase (hTrpRS) differs from its bacterial counterpart at several key positions of the catalytic active site and has an extra N-terminal domain, implying possibly a different catalytic mechanism. We report here the crystal structures of hTrpRS in complexes with Trp, tryptophanamide and ATP and tryptophanyl-AMP, respectively, which represent three different enzymatic states of the Trp activation reaction. Analyses of these structures reveal the molecular basis of the mechanisms of the substrate recognition and the activation reaction. The dimeric hTrpRS is structurally and functionally asymmetric with half-of-the-sites reactivity. Recognition of Trp is by an induced-fit mechanism involving conformational change of the AIDQ motif that creates a perfect pocket for the binding and activation of Trp and causes coupled movements of the N-terminal and C-terminal domains. The KMSAS loop appears to have an inherent flexibility and the binding of ATP stabilizes it in a closed conformation that secures the position of ATP for catalysis. Our structural data indicate that the catalytic mechanism of the Trp activation reaction by hTrpRS involves more moderate conformational changes of the structural elements at the active site to recognize and bind the substrates, which is more complex and fine-tuned than that of bacterial TrpRS.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18180246}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18180246 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18180246}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Protein biosynthesis]] | | [[Category: Protein biosynthesis]] |
| [[Category: Rossmann fold]] | | [[Category: Rossmann fold]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:17:23 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:07:53 2008'' |