Homoisocitrate dehydrogenase is involved in the alpha-aminoadipate pathway of biosynthesis of l-lysine in fungi, yeast, some prokaryotic bacteria, and archaea. This enzyme catalyzes the oxidative decarboxylation of (2R,3S)-homoisocitrate into 2-oxoadipate using NAD(+) as a coenzyme. Substrate specificity of two homoisocitrate dehydrogenases derived from Deinococcus radiodurans and Saccharomyces more ..
Target
| Sequence: RecName: Full=Homoisocitrate dehydrogenase, mitochondrial; Flags: Precursor Description ..   Protein Family: LeuB Comment .. Gene:LYS12 Related Protein 3D Structures |
BioActive Compounds: 2
Description:
Title: Substrate specificity analysis and inhibitor design of homoisocitrate dehydrogenase.
Abstract: Homoisocitrate dehydrogenase is involved in the alpha-aminoadipate pathway of biosynthesis of l-lysine in fungi, yeast, some prokaryotic bacteria, and archaea. This enzyme catalyzes the oxidative decarboxylation of (2R,3S)-homoisocitrate into 2-oxoadipate using NAD(+) as a coenzyme. Substrate specificity of two homoisocitrate dehydrogenases derived from Deinococcus radiodurans and Saccharomyces cerevisiae was analyzed using a series of synthetic substrate analogs, which indicated a relatively broad substrate specificity of these enzymes. Based on the substrate specificity, 3-hydroxyalkylidene- and 3-carboxyalkylidenemalate derivatives were designed as a specific inhibitor for homoisocitrate dehydrogenase. The synthetic inhibitors showed a moderate competitive inhibitory activity and (R,Z)-3-carboxypropylidenemalate was the most inhibitory among the synthesized inhibitors. Therefore, homoisocitrate dehydrogenase appeared to recognize preferentially an extended conformation of homoisocitrate.
(PMID: 17116397)
Abstract: Homoisocitrate dehydrogenase is involved in the alpha-aminoadipate pathway of biosynthesis of l-lysine in fungi, yeast, some prokaryotic bacteria, and archaea. This enzyme catalyzes the oxidative decarboxylation of (2R,3S)-homoisocitrate into 2-oxoadipate using NAD(+) as a coenzyme. Substrate specificity of two homoisocitrate dehydrogenases derived from Deinococcus radiodurans and Saccharomyces cerevisiae was analyzed using a series of synthetic substrate analogs, which indicated a relatively broad substrate specificity of these enzymes. Based on the substrate specificity, 3-hydroxyalkylidene- and 3-carboxyalkylidenemalate derivatives were designed as a specific inhibitor for homoisocitrate dehydrogenase. The synthetic inhibitors showed a moderate competitive inhibitory activity and (R,Z)-3-carboxypropylidenemalate was the most inhibitory among the synthesized inhibitors. Therefore, homoisocitrate dehydrogenase appeared to recognize preferentially an extended conformation of homoisocitrate.
(PMID: 17116397)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 102958
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 102958
ChEMBL target type: Target is a single protein chain
Result Definitions
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| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Km* | Km PubChem standard value |  | Float | μM | |
| 2 | Kcat activity comment | Kcat activity comment | String | |||
| 3 | Kcat standard flag | Kcat standard flag | | Integer | ||
| 4 | Kcat qualifier | Kcat qualifier | String | |||
| 5 | Kcat published value | Kcat published value | | Float | s-1 | |
| 6 | Kcat standard value | Kcat standard value | | Float | s-1 | |
| 7 | Km activity comment | Km activity comment | String | |||
| 8 | Km standard flag | Km standard flag | | Integer | ||
| 9 | Km qualifier | Km qualifier | String | |||
| 10 | Km published value | Km published value | | Float | nM | |
| 11 | Km standard value | Km standard value | | Float | nM |
* Activity Concentration.
Data Table (Concise)
Classification
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