Homology of lysosomal enzymes and related proteins: Prediction of posttranslational modification sites including phosphorylation of mannose and potential epitopic and substrate binding sites in the α- and β-subunits of hexosaminidases, α-glucosidase, and rabbit and human isomaltase

1988 ◽  
Vol 4 (3) ◽  
pp. 182-189 ◽  
Author(s):  
Alison K. Barnes ◽  
Colin H. Wynn
Keyword(s):  
Posttranslational Modification ◽  
Binding Sites ◽  
Lysosomal Enzymes ◽  
Substrate Binding ◽  
Α And Β Subunits ◽  
Substrate Binding Sites ◽  
Related Proteins

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.

Chemical mechanism and substrate binding sites of NADP-dependent aldehyde dehydrogenase from Streptococcus mutans

2001 ◽  
Vol 130-132 ◽  
pp. 15-28 ◽  
Author(s):  
Stéphane Marchal ◽  
David Cobessi ◽  
Sophie Rahuel-Clermont ◽  
Frédérique Tête-Favier ◽  
André Aubry ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Aldehyde Dehydrogenase ◽  
Binding Sites ◽  
Substrate Binding ◽  
Chemical Mechanism ◽  
Substrate Binding Sites
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