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Molybdenum oxide/bipyridine hybrid materials: synthesis, structure and catalytic studies
| Content Provider | Semantic Scholar |
|---|---|
| Author | Amarante, Tatiana R. Abrantes, Marta Antunes, Margarida M. Gago, Sandra Paz, Filipe A. Almeida Pillinger, Martyn Valente, Anabela A. Gonçalves, Isabel S. |
| Copyright Year | 2011 |
| Abstract | C435 crystal structure of human T-protein with folate cofactor and provided the insight into the molecular basis of the disease-causing mutations. Here we present the crystal structure of Escherichia coli T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate (5CH3-THF): a complex mimicking the ternary complex in the reverse reaction. The structure of the complex shows a highly interacting intermolecular interface limited to a small area and the protein-bound dihydrolipoyllysine arm inserted into the active site cavity of the Tprotein. Among the residues contributing to the interface, invariant Arg292 of the T-protein plays a key role in the complex assembly and probably in recruiting the aminomethyllipoyllysine arm to the active site of T-protein. It has been speculated that the aminomethyltransfer reaction from aminomethyllipoate of H-intermediate to THF is initiated by the direct attack of the methylene carbon atom by the nucleophilic N5 or N10 atoms of THF bound to T-protein accompanying the release of ammonia. However, the distances between the tip of the dihydrolipoyllysine arm and the methyl carbon atom of 5-CH3THF observed in the complex structure suggests the presence of an intermediary mediating the transfer reaction rather than the direct interaction. The hydrogen bond network surrounding the S8 atom of the dihydrolipoyllysine including invariant Asp96, Asp97, Asn113, and Arg223 of T-protein suggests that the reversible transfer of the methylene group between the lipoate and tetrahydrofolate should proceed through the electron relay-assisted iminium intermediate formation. Based on the structural observations together with mutational analyses, we propose a possible mechanism for T-protein catalysis. The structure also provides novel insights in understanding the disease-causing mutations, in addition to the disease-related impairment in the cofactor-enzyme interactions presented previously. |
| Starting Page | 435 |
| Ending Page | 435 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| DOI | 10.1107/S0108767311089070 |
| Volume Number | 67 |
| Alternate Webpage(s) | http://journals.iucr.org/a/issues/2011/a1/00/a47693/a47693.pdf |
| Alternate Webpage(s) | https://doi.org/10.1107/S0108767311089070 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
