1s3i

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{{STRUCTURE_1s3i| PDB=1s3i | SCENE= }}
{{STRUCTURE_1s3i| PDB=1s3i | SCENE= }}
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'''Crystal structure of the N terminal hydrolase domain of 10-formyltetrahydrofolate dehydrogenase'''
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===Crystal structure of the N terminal hydrolase domain of 10-formyltetrahydrofolate dehydrogenase===
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==Overview==
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10-Formyltetrahydrofolate dehydrogenase (FDH) converts 10-formyltetrahydrofolate, a precursor for nucleotide biosynthesis, to tetrahydrofolate. The protein comprises two functional domains: a hydrolase domain that removes a formyl group from 10-formyltetrahydrofolate and a NADP(+)-dependent dehydrogenase domain that reduces the formyl to carbon dioxide. As a first step toward deciphering the catalytic mechanism of the enzyme, we have determined the crystal structure of the hydrolase domain of FDH from rat, solved to 2.3-A resolution. The structure comprises two domains. As expected, domain 1 shares the same Rossmann fold as the related enzymes, methionyl-tRNA-formyltransferase and glycinamide ribonucleotide formyltransferase, but, unexpectedly, the structural similarity between the amino-terminal domain of 10-formyltetrahydrofolate dehydrogenase and methionyl-tRNA-formyltransferase extends to the C terminus of both proteins. The active site contains a molecule of beta-mercaptoethanol that is positioned between His-106 and Asp-142 and that appears to mimic the formate product. We propose a catalytic mechanism for the hydrolase reaction in which Asp-142 polarizes the catalytic water molecule and His-106 orients the carbonyl group of formyl. The structure also provides clues as to how, in the native enzyme, the hydrolase domain transfers its product to the dehydrogenase domain.
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(as it appears on PubMed at http://www.pubmed.gov), where 14729668 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14729668}}
==About this Structure==
==About this Structure==
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[[Category: Krupenko, S A.]]
[[Category: Krupenko, S A.]]
[[Category: Rossmann fold]]
[[Category: Rossmann fold]]
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Revision as of 17:16, 27 July 2008

Template:STRUCTURE 1s3i

Crystal structure of the N terminal hydrolase domain of 10-formyltetrahydrofolate dehydrogenase

Template:ABSTRACT PUBMED 14729668

About this Structure

1S3I is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain., Chumanevich AA, Krupenko SA, Davies C, J Biol Chem. 2004 Apr 2;279(14):14355-64. Epub 2004 Jan 16. PMID:14729668

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