| Title: |
Acinetobacter baumannii Fol Dligand complexes – potent inhibitors of folate metabolism and a re‐evaluation of the structure of LY374571 |
| Authors: |
Eadsforth, Thomas C.; Maluf, Fernando V.; Hunter, William N. |
| Source: |
The FEBS Journal ; volume 279, issue 23, page 4350-4360 ; ISSN 1742-464X 1742-4658 |
| Publisher Information: |
Wiley |
| Publication Year: |
2012 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
The bifunctional N 5 , N 10 ‐methylenetetrahydrofolate dehydrogenase/cyclohydrolase ( DHCH or FolD), which is widely distributed in prokaryotes and eukaryotes, is involved in the biosynthesis of folate cofactors that are essential for growth and cellular development. The enzyme activities represent a potential antimicrobial drug target. We have characterized the kinetic properties of FolD from the Gram‐negative pathogen Acinetobacter baumanni and determined high‐resolution crystal structures of complexes with a cofactor and two potent inhibitors. The data reveal new details with respect to the molecular basis of catalysis and potent inhibition. A unexpected finding was that our crystallographic data revealed a different structure for LY 374571 (an inhibitor studied as an antifolate) than that previously published. The implications of this observation are discussed. Database The coordinates have been deposited in the Protein Data Bank under accession numbers: 4B4U , 4B4V and 4B4W . Structured digital abstract AbFolD and AbFolD bind by x-ray crystallography ( View interaction ) |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/febs.12025 |
| Availability: |
https://doi.org/10.1111/febs.12025; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Ffebs.12025; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/febs.12025 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.999A58B8 |
| Database: |
BASE |