scholarly journals Structures and mechanism of the monoamine oxidase family

2011 ◽  
Vol 2 (5) ◽  
pp. 365-377 ◽  
Author(s):  
Helena Gaweska ◽  
Paul F. Fitzpatrick
Keyword(s):  
Monoamine Oxidase ◽  
Binding Sites ◽  
Flavin Adenine Dinucleotide ◽  
Catalytic Reactions ◽  
Secondary Amines ◽  
Binding Domains ◽  
The Family ◽  
Substrate Binding Sites ◽  
Fad Binding ◽  
Methylated Lysine

AbstractMembers of the monoamine oxidase family of flavoproteins catalyze the oxidation of primary and secondary amines, polyamines, amino acids, and methylated lysine side chains in proteins. The enzymes have similar overall structures, with conserved flavin adenine dinucleotide (FAD)-binding domains and varied substrate-binding sites. Multiple mechanisms have been proposed for the catalytic reactions of these enzymes. The present review compares the structures of different members of the family and the various mechanistic proposals.

scholarly journals Structural comparison of p-hydroxybenzoate hydroxylase (PobA) from Pseudomonas putida with PobA from other Pseudomonas spp. and other monooxygenases

2019 ◽  
Vol 75 (7) ◽  
pp. 507-514
Author(s):  
John T. Lazar ◽  
Ludmilla Shuvalova ◽  
Monica Rosas-Lemus ◽  
Olga Kiryukhina ◽  
Karla J. F. Satchell ◽  
...  
Keyword(s):  
Pseudomonas Putida ◽  
Binding Sites ◽  
Drug Target ◽  
Tetracycline Resistance ◽  
Hydroxybenzoate Hydroxylase ◽  
Substrate Binding Sites ◽  
Key Residues ◽  
Polypeptide Chains ◽  
Β Sheet ◽  
Fad Binding

The crystal structure is reported of p-hydroxybenzoate hydroxylase (PobA) from Pseudomonas putida, a possible drug target to combat tetracycline resistance, in complex with flavin adenine dinucleotide (FAD). The structure was refined at 2.2 Å resolution with four polypeptide chains in the asymmetric unit. Based on the results of pairwise structure alignments, PobA from P. putida is structurally very similar to PobA from P. fluorescens and from P. aeruginosa. Key residues in the FAD-binding and substrate-binding sites of PobA are highly conserved spatially across the proteins from all three species. Additionally, the structure was compared with two enzymes from the broader class of oxygenases: 2-hydroxybiphenyl 3-monooxygenase (HbpA) from P. nitroreducens and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase (MHPCO) from Mesorhizobium japonicum. Despite having only 14% similarity in their primary sequences, pairwise structure alignments of PobA from P. putida with HbpA from P. nitroreducens and MHPCO from M. japonicum revealed local similarities between these structures. Key secondary-structure elements important for catalysis, such as the βαβ fold, β-sheet wall and α12 helix, are conserved across this expanded class of oxygenases.

FAD-BERT: Improved prediction of FAD binding sites using pre-training of deep bidirectional transformers

2021 ◽  
Vol 131 ◽  
pp. 104258
Author(s):  
Quang-Thai Ho ◽  
Trinh-Trung-Duong Nguyen ◽  
Nguyen Quoc Khanh Le ◽  
Yu-Yen Ou
Keyword(s):  
Binding Sites ◽  
Fad Binding

Substrate-binding sites in acetylcholinesterase

1991 ◽  
Vol 12 ◽  
pp. 422-426 ◽  
Author(s):  
Ferdinand Hucko ◽  
Jaak Järv ◽  
Christoph Weise
Keyword(s):  
Binding Sites ◽  
Substrate Binding ◽  
Substrate Binding Sites

scholarly journals Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites

2005 ◽  
Vol 288 (2) ◽  
pp. F327-F333 ◽  
Author(s):  
Rémon A. M. H. Van Aubel ◽  
Pascal H. E. Smeets ◽  
Jeroen J. M. W. van den Heuvel ◽  
Frans G. M. Russel
Keyword(s):  
Binding Sites ◽  
Efflux Pump ◽  
Substrate Binding ◽  
Organic Anion ◽  
Apical Cell ◽  
Cell Uptake ◽  
Hek293 Cells ◽  
Hill Coefficient ◽  
Anion Transporter ◽  
Substrate Binding Sites

The end product of human purine metabolism is urate, which is produced primarily in the liver and excreted by the kidney through a well-defined basolateral blood-to-cell uptake step. However, the apical cell-to-urine efflux mechanism is as yet unidentified. Here, we show that the renal apical organic anion efflux transporter human multidrug resistance protein 4 (MRP4), but not apical MRP2, mediates ATP-dependent urate transport via a positive cooperative mechanism ( Km of 1.5 ± 0.3 mM, Vmax of 47 ± 7 pmol·mg−1·min−1, and Hill coefficient of 1.7 ± 0.2). In HEK293 cells overexpressing MRP4, intracellular urate levels were lower than in control cells. Urate inhibited methotrexate transport (IC50 of 235 ± 8 μM) by MRP4, did not affect cAMP transport, whereas cGMP transport was stimulated. Urate shifted cGMP transport by MRP4 from positive cooperativity ( Km and Vmax value of 180 ± 20 μM and 58 ± 4 pmol·mg−1·min−1, respectively, Hill coefficient of 1.4 ± 0.1) to single binding site kinetics ( Km and Vmax value of 2.2 ± 0.9 mM and 280 ± 50 pmol·mg−1·min−1, respectively). Finally, MRP4 could transport urate simultaneously with cAMP or cGMP. We conclude that human MRP4 is a unidirectional efflux pump for urate with multiple allosteric substrate binding sites. We propose MRP4 as a candidate transporter for urinary urate excretion and suggest that MRP4 may also mediate hepatic export of urate into the circulation, because of its basolateral expression in the liver.

Sign in / Sign up

Export Citation Format

Share Document