1S3I
Crystal structure of the N terminal hydrolase domain of 10-formyltetrahydrofolate dehydrogenase
Summary for 1S3I
| Entry DOI | 10.2210/pdb1s3i/pdb |
| Descriptor | 10-formyltetrahydrofolate dehydrogenase, BETA-MERCAPTOETHANOL (3 entities in total) |
| Functional Keywords | rossmann fold, hydrolase, oxidoreductase |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cytoplasm: P28037 |
| Total number of polymer chains | 1 |
| Total formula weight | 34472.50 |
| Authors | Chumanevich, A.A.,Krupenko, S.A.,Davies, C. (deposition date: 2004-01-13, release date: 2004-01-27, Last modification date: 2021-10-27) |
| Primary citation | Chumanevich, A.A.,Krupenko, S.A.,Davies, C. The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain. J.Biol.Chem., 279:14355-14364, 2004 Cited by PubMed Abstract: 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. PubMed: 14729668DOI: 10.1074/jbc.M313934200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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