3POA
Structural and functional analysis of phosphothreonine-dependent FHA domain interactions
Summary for 3POA
| Entry DOI | 10.2210/pdb3poa/pdb |
| Related | 3PO8 |
| Descriptor | Putative uncharacterized protein TB39.8, synthetic phosphopeptide, ZINC ION, ... (4 entities in total) |
| Functional Keywords | fha domain, synthetic phosphopeptide, peptide binding protein |
| Biological source | Mycobacterium tuberculosis More |
| Total number of polymer chains | 2 |
| Total formula weight | 12460.04 |
| Authors | Pennell, S.,Smerdon, S.J. (deposition date: 2010-11-22, release date: 2011-01-26, Last modification date: 2024-11-13) |
| Primary citation | Pennell, S.,Westcott, S.,Ortiz-Lombardia, M.,Patel, D.,Li, J.,Nott, T.J.,Mohammed, D.,Buxton, R.S.,Yaffe, M.B.,Verma, C.,Smerdon, S.J. Structural and functional analysis of phosphothreonine-dependent FHA domain interactions Structure, 18:1587-1595, 2010 Cited by PubMed Abstract: FHA domains are well established as phospho-dependent binding modules mediating signal transduction in Ser/Thr kinase signaling networks in both eukaryotic and prokaryotic species. Although they are unique in binding exclusively to phosphothreonine, the basis for this discrimination over phosphoserine has remained elusive. Here, we attempt to dissect overall binding specificity at the molecular level. We first determined the optimal peptide sequence for Rv0020c FHA domain binding by oriented peptide library screening. This served as a basis for systematic mutagenic and binding analyses, allowing us to derive relative thermodynamic contributions of conserved protein and peptide residues to binding and specificity. Structures of phosphopeptide-bound and uncomplexed Rv0020c FHA domain then directed molecular dynamics simulations which show how the extraordinary discrimination in favor of phosphothreonine occurs through formation of additional hydrogen-bonding networks that are ultimately stabilized by van der Waals interactions of the phosphothreonine γ-methyl group with a conserved pocket on the FHA domain surface. PubMed: 21134638DOI: 10.1016/j.str.2010.09.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.01 Å) |
Structure validation
Download full validation report
