PDBsum entry 3smb

Isomerase/isomerase inhibitor

PDB id: 3smb

Contents

Protein chains

114 a.a.

Ligands

LE2 ×3

Metals

_NA ×3

_CL ×9

Waters ×435

PDB id:

3smb

Name:

Isomerase/isomerase inhibitor

Title:

Phenethylisothiocyanate covalently bound to macrophage migration inhibitory factor (mif)

Structure:

Macrophage migration inhibitory factor. Chain: a, b, c. Synonym: mif, glycosylation-inhibiting factor, gif, l-dopachrome isomerase, l-dopachrome tautomerase, phenylpyruvate tautomerase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: glif, mif, mmif. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.181 R-free: 0.197

Authors:

G.V.Crichlow,E.J.Lolis

Key ref:

G.V.Crichlow et al. (2012). Structural interactions dictate the kinetics of macrophage migration inhibitory factor inhibition by different cancer-preventive isothiocyanates. Biochemistry, 51, 7506-7514. PubMed id: 22931430

Date:

27-Jun-11 Release date: 03-Oct-12

Protein chains

P14174  (MIF_HUMAN) -  Macrophage migration inhibitory factor from Homo sapiens

Seq: 115 a.a.

Struc: 114 a.a.

Enzyme reactions

• Enzyme class 2: E.C.5.3.2.1 - phenylpyruvate tautomerase.
• Reaction: 3-phenylpyruvate = enol-phenylpyruvate

3-phenylpyruvate = enol-phenylpyruvate (Bound ligand (Het Group name = LE2) matches with 53.33% similarity)

• Enzyme class 3: E.C.5.3.3.12 - L-dopachrome isomerase.

Pathway:

• Reaction: L-dopachrome = 5,6-dihydroxyindole-2-carboxylate

L-dopachrome (Bound ligand (Het Group name = LE2) matches with 56.25% similarity) = 5,6-dihydroxyindole-2-carboxylate

• Cofactor: Zn(2+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Biochemistry 51:7506-7514 (2012)

PubMed id: 22931430

Structural interactions dictate the kinetics of macrophage migration inhibitory factor inhibition by different cancer-preventive isothiocyanates.

G.V.Crichlow, C.Fan, C.Keeler, M.Hodsdon, E.J.Lolis.

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.