4KJK

Room Temperature WT DHFR

Summary for 4KJK

• Entry DOI: 10.2210/pdb4kjk/pdb
• Related: 4KJJ 4KJL
• Descriptor: Dihydrofolate reductase, FOLIC ACID, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 19284.30

Authors

van den Bedem, H.,Bhabha, G.,Yang, K.,Wright, P.E.,Fraser, J.S. (deposition date: 2013-05-03, release date: 2013-08-21, Last modification date: 2024-02-28)

Primary citation

van den Bedem, H.,Bhabha, G.,Yang, K.,Wright, P.E.,Fraser, J.S.
Automated identification of functional dynamic contact networks from X-ray crystallography.
Nat.Methods, 10:896-902, 2013

PubMed Abstract: 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.

PubMed: 23913260
DOI: 10.1038/nmeth.2592

Experimental method

X-RAY DIFFRACTION (1.351 Å)