Loop conformation and dynamics of the Escherichia coli HPPK apo-enzyme and its binary complex with MgATP.

ABSTRACT: Comparison of the crystallographic and NMR structures of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) suggests that the enzyme may undergo significant conformational change upon binding to its first substrate, ATP. Two of the three surface loops (loop 2 and loop 3) accounting for most of the conformational differences appear to be confined by crystal contacts, raising questions about the putative large-scale induced-fit conformational change of HPPK and the functional roles of the conserved side-chain residues on the loops. To investigate the loop dynamics in crystal-free environment, we carried out molecular dynamics and locally enhanced sampling simulations of the apo-enzyme and the HPPK.MgATP complex. Our simulations showed that the crystallographic B-factors underestimate

SUBMITTER: Yang R 

PROVIDER: S-EPMC1366583 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature