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Title: Crystallographic and Molecular Dynamics Simulation Analysis of Escherichia Coli Dihydroneopterin Aldolase

To understand the structural basis for the biochemical differences and further investigate the catalytic mechanism of DHNA, we have determined the structure of EcDHNA complexed with NP at 1.07-Å resolution [PDB:2O90], built an atomic model of EcDHNA complexed with the substrate DHNP, and performed molecular dynamics (MD) simulation analysis of the substrate complex. EcDHNA has the same fold as SaDHNA and also forms an octamer that consists of two tetramers, but the packing of one tetramer with the other is significantly different between the two enzymes. Furthermore, the structures reveal significant differences in the vicinity of the active site, particularly in the loop that connects strands β3 and β4, mainly due to the substitution of nearby residues. The building of an atomic model of the complex of EcDHNA and the substrate DHNP and the MD simulation of the complex show that some of the hydrogen bonds between the substrate and the enzyme are persistent, whereas others are transient. The substrate binding model and MD simulation provide the molecular basis for the biochemical behaviors of the enzyme, including noncooperative substrate binding, indiscrimination of a pair of epimers as the substrates, proton wire switching during catalysis, and formation of epimerization product.
 [1] ;  [2] ;  [2] ;  [2] ;  [3]
  1. National Cancer Inst., Frederick, MD (United States); Michigan State Univ., East Lansing, MI (United States)
  2. Michigan State Univ., East Lansing, MI (United States)
  3. National Cancer Inst., Frederick, MD (United States)
Publication Date:
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 2045-3701
DOE Contract Number:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell & Bioscience; Journal Volume: 4
BioMed Central
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES Dihydroneopterin aldolase; DHNA; structure; dynamics; catalysis