Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis.
- Zhengfan Jiang, P. Georgel, B. Beutler
- BiologyProceedings of the National Academy of Sciences…
- 18 July 2006
The immunovariant N-ethyl-N-nitrosourea-induced mutations Pococurante (Poc) and Lackadaisical were found to alter MyD 88, creating striking receptor-selective effects, and the TIR domain surface that mediates association between TLRs and MyD88 and the surface required for MyD87 or TLR oligomerization is defined.
Downstream regulator TANK binds to the CD40 recognition site on TRAF3.
LMP1 Protein from the Epstein-Barr Virus Is a Structural CD40 Decoy in B Lymphocytes for Binding to TRAF3*
The crystal structure of this portion of L MP1 C-terminal activation region-1 (204PQQATDD210) bound in complex with TRAF3 is reported, providing a molecular mechanism for LMP1 to act as a CD40 decoy for TRAF 3, influencing downstream signaling to B lymphocytes and contributing to dysregulated signaling by LMP 1.
Structurally Distinct Recognition Motifs in Lymphotoxin-β Receptor and CD40 for Tumor Necrosis Factor Receptor-associated Factor (TRAF)-mediated Signaling*
The results reveal structurally adaptive “hot spots” in the TRAF3-binding crevice that promote molecular interactions driving specific signaling after contact with LTβR, CD40, or the downstream regulator TANK.
Structural Analysis of Siah1 and Its Interactions with Siah-interacting Protein (SIP)*
- S. Matsuzawa, Chenglong Li, C. Ni, S. Takayama, John Calvin Reed, K. R. Ely
- Biology, ChemistryThe Journal of Biological Chemistry
- 17 January 2003
A structure-based approach was used to identify interacting residues in Siah that are required for association with SIP, and the structural prediction was confirmed by site-directed mutagenesis of these electronegative residues, resulting in loss of binding of Siah1 to SIP in vitro and in cells.
Comparative Docking Assessment of Glucokinase Interactions with its Allosteric Activators
Comparison docking assessment using Autodock4 revealed that the three arms of Glucokinase activators bind to three aromatic/hydrophobic subpockets at the allosteric site, which has the best potential for further GKA optimization by utilizing aromatic heterocycles and hydrogen bond forming linkers to build the GKA 2nd arm.
Virtual screening of human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase against the NCI diversity set by use of AutoDock to identify novel nonfolate inhibitors.
- Chenglong Li, Lan Xu, D. Wolan, I. Wilson, A. Olson
- Biology, ChemistryJournal of medicinal chemistry
- 2 December 2004
These 19 inhibitors serve as novel templates/scaffolds for development of more potent and specific non-folate-based AICAR transformylase inhibitors.
Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid.
A structure-based approach is used to design a novel folate analogue, 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid (10-CF(3)CO-DDACTHF, 1), which specifically inhibits recombinant human GAR Tfase and is a potent inhibitor of tumor cell proliferation.
Conformational restrictions in the active site of unliganded human caspase‐3
- C. Ni, Chenglong Li, Joe C. Wu, A. Spada, K. R. Ely
- Chemistry, BiologyJournal of Molecular Recognition
- 1 May 2003
The crystal structure of the unoccupied substrate‐binding site of caspase‐3 is presented and reveals critical side chain movements in a hydrophobic pocket in the active site.
The Serine-rich Domain from Crk-associated Substrate (p130cas) Is a Four-helix Bundle*
The solution structure of the serine-rich region has been determined by NMR spectroscopy, demonstrating that this is a stable domain that folds as a four-helix bundle, a protein-interaction motif.