4KJL: Room Temperature N23pps148a Dhfr

Protein function often depends on the exchange between conformational substates. Allosteric ligand binding or distal mutations can stabilize specific active-site conformations and consequently alter protein function. Observing alternative conformations at low levels of electron density, in addition to comparison of independently determined X-ray crystal structures, can provide mechanistic insights into conformational dynamics. Here we report a new algorithm, CONTACT, that identifies contact networks of conformationally heterogeneous residues directly from high-resolution X-ray crystallography data. Contact networks determined for Escherichia coli dihydrofolate reductase (ecDHFR) predict the observed long-range pattern of NMR chemical shift perturbations of an allosteric mutation. A comparison of contact networks in wild-type and mutant ecDHFR suggests that mutations that alter optimized contact networks of coordinated motions can impair catalytic function. CONTACT-guided mutagenesis can exploit the structure-dynamics-function relationship in protein engineering and design.
PDB ID: 4KJLDownload
MMDB ID: 112835
PDB Deposition Date: 2013/5/3
Updated in MMDB: 2014/11 
Experimental Method:
x-ray diffraction
Resolution: 1.38  Å
Source Organism:
Similar Structures:
Biological Unit for 4KJL: monomeric; determined by author and by software (PISA)
Molecular Components in 4KJL
Label Count Molecule
Protein (1 molecule)
Dihydrofolate Reductase
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB