• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

J Biol Inorg Chem 2016 Oct;21(7):875-86

Corynebacterium diphtheriae HmuT: dissecting the roles of conserved residues in heme pocket stabilization.

Draganova EB, Adrian SA, Lukat-Rodgers GS, Keutcha CS, Schmitt MP, Rodgers KR, Dixon DW


The heme-binding protein HmuT is part of the Corynebacterium diphtheriae heme uptake pathway and is responsible for the delivery of heme to the HmuUV ABC transporter. HmuT binds heme with a conserved His/Tyr heme axial ligation motif. Sequence alignment revealed additional conserved residues of potential importance for heme binding: R237, Y272 and M292. In this study, site-directed mutations at these three positions provided insight into the nature of axial heme binding to the protein and its effect on the thermal stability of the heme-loaded protein fold. UV-visible absorbance, resonance Raman (rR) and thermal unfolding experiments, along with collision-induced dissociation electrospray ionization mass spectrometry, were used to probe the contributions of each mutated residue to the stability of varpi HmuT. Thermal unfolding and rR experiments revealed that R237 and M292 are important residues for heme binding. Arginine 237 is a hydrogen-bond donor to the phenol side chain of Y235, which serves as an axial heme ligand. Methionine 292 serves a supporting structural role, favoring the R237 hydrogen-bond donation, which elicits a, heretofore, unobserved modulating influence on pi donation by the axial tyrosine ligand in the heme carbonyl complex, HmuT-CO.

Category: Journal Article
PubMed ID: #27561288 DOI: 10.1007/s00775-016-1386-3
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2016-08-29 Entry Last Modified: 2016-11-12