BibTex format
°ª²¹°ù³Ù¾±³¦±ô±ðµ÷³§³¦³ó°ùö»å±ð°ù:2026:10.1002/±è°ù´Ç.70666,
author = {Schröder, GC and Crichlow, GV and Jablonowski, E and Pantouris, G and Nix, J and Chayen, N and Meilleur, F and Lolis, EJ},
doi = {10.1002/pro.70666},
journal = {Protein Science},
title = {Identification of a key water molecule involved in the macrophage migration inhibitory factorcatalyzed tautomerization of parahydroxyphenylpyruvate using neutron crystallography},
url = {http://dx.doi.org/10.1002/pro.70666},
volume = {35},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Neutron crystallography was used to determine a 2.5-Å resolution all-atom structure of macrophage migration inhibitory factor (MIF) interacting with 3-(4-hydroxyphenyl)-pyruvate (HPP). MIF is a pro-inflammatory, pro-tumorigenic protein that may be an attractive therapeutic target. MIF catalyzes the interconversion of the keto and enol forms of HPP by a tautomerase reaction. Although HPP is evidently not a physiological substrate of MIF, many compounds that inhibit this activity in enzymatic assays have been found also to inhibit physiological activities of MIF. Therefore, the MIF-catalyzed HPP tautomerization reaction is used in initial screening of compounds in the search for inhibitors of MIF physiological activity. The neutron diffraction-derived crystal structure reveals the position of a water molecule involved in the tautomerization reaction, and also confirms the charged state of lysine-32 in the active site. The structure confirms the previously proposed catalytic mechanism of MIF, with the N-terminal Pro-1 abstracting a proton to generate an HPP enolate intermediate which is subsequently protonated. The structure reported herein reveals that this proton is supplied by a neighboring water molecule. Along with the neutron structure, a room-temperature synchrotron x-ray crystal structure reveals a covalent adduct between HPP and MIF. While this adduct is a result of radiation-induced chemistry, its formation confirms the catalytic role of the active site residue because a covalent complex could only form if the reactive carbon of the substrate is correctly positioned by the enzyme.
AU - Schröder,GC
AU - Crichlow,GV
AU - Jablonowski,E
AU - Pantouris,G
AU - Nix,J
AU - Chayen,N
AU - Meilleur,F
AU - Lolis,EJ
DO - 10.1002/pro.70666
PY - 2026///
SN - 0961-8368
TI - Identification of a key water molecule involved in the macrophage migration inhibitory factorcatalyzed tautomerization of parahydroxyphenylpyruvate using neutron crystallography
T2 - Protein Science
UR - http://dx.doi.org/10.1002/pro.70666
UR - https://doi.org/10.1002/pro.70666
VL - 35
ER -