PDBsum entry 1jnq

Oxidoreductase

PDB id: 1jnq

Contents

Protein chain

849 a.a. *

Ligands

EGT

Metals

FE2

Waters ×512

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Inhibition of lipoxygenase by (-)-Epigallocatechin gallate: x-Ray analysis at 2.1 a reveals degradation of egcg and shows soybean lox-3 complex with egc instead.
• Authors: E.Skrzypczak-Jankun, K.Zhou, J.Jankun.
• Ref.: Int J Mol Med, 2003, 12, 415-420.
• PubMed id: 12964012

Abstract

Lipoxygenases (LOXs) are non-heme iron containing enzymes ubiquitous in nature and participating in the metabolism of the polyunsaturated fatty acids (PUFA). They are capable of combining their dioxygenase activity with its co-oxidative activity manifesting itself in biotransformation reactions catalyzed by LOXs for other than PUFA small molecules. LOXs involvement in inflammatory diseases and cancer have been well documented. Catechins are the natural flavonoids of known inhibitory activity toward dioxygenases with a potential to be utilized in disease prevention and treatment. This work presents results obtained from an X-ray analysis of (-)-epigallocatechin gallate (EGCG) interacting with soybean lipoxygenase-3. The 3D structure of the resulting complex reveals the inhibitor depicting (-)-epigallo-catechin that lacks galloyl moiety. The A-ring is near the iron co-factor, attached by the hydrogen bond to the C-terminus of the enzyme, and the B-ring hydroxyl groups participate in the hydrogen bonds and the van der Waals interactions formed by the surrounding amino acids and water molecules.

Secondary reference #1

• Title: Why drinking green tea could prevent cancer.
• Authors: J.Jankun, S.H.Selman, R.Swiercz, E.Skrzypczak-Jankun.
• Ref.: Nature, 1997, 387, 561. [DOI no: 10.1038/42381]
• PubMed id: 9177339

Figure 1.
Figure 1 Connolly surface of uPA showing the catalytic triad His 57, Asp 102 and Ser 195 (red) at the bottom, and Arg 35, Arg A37 (blue) at the brim, of the cavity. EGCG, well fitted into this cavity, is shown as a 'stick model' in green (C), red (O) and white (H). The calculated energy of intermolecular interaction between EGCG and uPA is -116.81 kcal mol-1; LUDI score, 498; calculated K[i], 1.04 10^-5 M. b, Cleavage of Spectrozyme by uPA in the presence of EGCG (inset) from Sigma (blue triangles), and from MayBridge, UK (purple diamonds); amiloride (green squares), and control sample (orange circles). Experimental mixtures (50 mM Tris with 0.01% Tween 80, 0.01% PEG 8000 buffer; pH 8.8) were incubated with 1 g of uPA and decreasing amounts of inhibitor for 15 min. 100 l of this mixture was incubated in a 96-well microplate with 50 l (2.5 mM) Spectrozyme (carbobenzyl-L-( )-Glu( -t-BuO)-Gly-Arg-p-nitroanilide.2C[2]H[5]OH from American Diagnostica Inc., Greenwich, Connecticut), for 10 min. Absorbance, which is inversely proportional to the uPA inhibitory activity7, was measured at 405 nm on a microplate reader.

The above figure is reproduced from the cited reference with permission from Macmillan Publishers Ltd

Secondary reference #2

• Title: Structural and thermochemical characterization of lipoxygenase-Catechol complexes.
• Authors: C.Pham, J.Jankun, E.Skrzypczak-Jankun, R.A.Flowers, M.O.Funk.
• Ref.: Biochemistry, 1998, 37, 17952-17957. [DOI no: 10.1021/bi981989t]
• PubMed id: 9922163

Secondary reference #3

• Title: Structure of soybean lipoxygenase l3 and a comparison with its l1 isoenzyme.
• Authors: E.Skrzypczak-Jankun, L.M.Amzel, B.A.Kroa, M.O.Funk.
• Ref.: Proteins, 1997, 29, 15-31.
• PubMed id: 9294864

Secondary reference #4

• Title: Position 713 is critical for catalysis but not iron binding in soybean lipoxygenase 3.
• Authors: J.A.Kramer, K.R.Johnson, W.R.Dunham, R.H.Sands, M.O.Funk.
• Ref.: Biochemistry, 1994, 33, 15017-15022. [DOI no: 10.1021/bi00254a010]
• PubMed id: 7999759