 |
PDBsum entry 3smb
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Isomerase/isomerase inhibitor
|
PDB id
|
|
|
|
3smb
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural interactions dictate the kinetics of macrophage migration inhibitory factor inhibition by different cancer-Preventive isothiocyanates.
|
|
|
Authors
|
|
G.V.Crichlow,
C.Fan,
C.Keeler,
M.Hodsdon,
E.J.Lolis.
|
|
|
Ref.
|
|
Biochemistry, 2012,
51,
7506-7514.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Regulation of cellular processes by dietary nutrients is known to affect the
likelihood of cancer development. One class of cancer-preventive nutrients,
isothiocyanates (ITCs), derived from the consumption of cruciferous vegetables,
is known to have various effects on cellular biochemistry. One target of ITCs is
macrophage migration inhibitory factor (MIF), a widely expressed protein with
known inflammatory, pro-tumorigenic, pro-angiogenic, and anti-apoptotic
properties. MIF is covalently inhibited by a variety of ITCs, which in part may
explain how they exert their cancer-preventive effects. We report the
crystallographic structures of human MIF bound to phenethylisothiocyanate and to
l-sulforaphane (dietary isothiocyanates derived from watercress and broccoli,
respectively) and correlate structural features of these two isothiocyanates
with their second-order rate constants for MIF inactivation. We also
characterize changes in the MIF structure using nuclear magnetic resonance
heteronuclear single-quantum coherence spectra of these complexes and observe
many changes at the subunit interface. While a number of chemical shifts do not
change, many of those that change do not have features similar in magnitude or
direction for the two isothiocyanates. The difference in the binding modes of
these two ITCs provides a means of using structure-activity relationships to
reveal insights into MIF biological interactions. The results of this study
provide a framework for the development of therapeutics that target MIF.
|
|
|
|
|
|
|
