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BioAssay: AID 387526

Activation of human recombinant CA1 after 15 mins by stopped-flow CO2 hydration assay

An activation study of mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms I-XIV with D- and L-tryptophan has been performed both by means of kinetic and X-ray crystallographic techniques. These compounds show a time dependent activity against isozyme CA II, with activation constants of 1.13 microM for L-Trp and 0.37 microM for D-Trp, respectively, after 24 h of incubation between enzyme and more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Active(3)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Active(3)
 
 
AID: 387526
Data Source: ChEMBL (535555)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2014-05-26

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Carbonic anhydrase 1; AltName: Full=Carbonate dehydratase I; AltName: Full=Carbonic anhydrase B; Short=CAB; AltName: Full=Carbonic anhydrase I; Short=CA-I
Description ..   
Protein Family: alpha_CA_I_II_III_XIII
Comment ..   

Gene:CA1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 3
Description:
Title: Carbonic anhydrase activators: kinetic and X-ray crystallographic study for the interaction of D- and L-tryptophan with the mammalian isoforms I-XIV.

Abstract: An activation study of mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms I-XIV with D- and L-tryptophan has been performed both by means of kinetic and X-ray crystallographic techniques. These compounds show a time dependent activity against isozyme CA II, with activation constants of 1.13 microM for L-Trp and 0.37 microM for D-Trp, respectively, after 24 h of incubation between enzyme and activator. The high resolution X-ray crystal structure of the hCA II-D-Trp adduct revealed the activator to bind in a totally unprecedented way to the enzyme active site as compared to histamine, L-/D-Phe, L-/D-His or L-adrenaline. D-Trp is anchored at the edge of the CA II active site entrance, strongly interacting with amino acid residues Asp130, Phe131 and Gly132 as well as with a loop of a second symmetry related protein molecule from the asymmetric unit, by means of hydrogen bonds and several weak van der Waals interactions involving Glu234, Gly235, Glu236 and Glu238. Thus, a second activator binding site (B) within the CA II cavity has been detected, where only D-Trp was shown so far to bind, in addition to the activator binding site A, in which histamine, L-/D-Phe, and L-/D-His are bound. These findings explain the strong affinity of D-Trp for CA II and may be useful for designing novel classes of CA activators by using this compound as lead molecule.
(PMID: 18774300)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Target Type: Target is a single protein chain

Protein Target Class: enzyme lyase

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ka activity commentKa activity commentString
2Ka standard flagKa standard flagInteger
3Ka qualifierKa qualifierString
4Ka published valueKa published valueFloatμM
5Ka standard valueKa standard valueFloatnM

Data Table (Concise)
Classification
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