Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DMEN263)
DME Name 3-MG-CoA hydratase (AUH), Homo sapiens
Gene Name AUH
UniProt ID
AUHM_HUMAN
EC Number    EC: 4.2.1.18     (Click to Show/Hide the Complete EC Tree)
Lyases
Carbon-oxygen lyase
Hydro-lyase
EC: 4.2.1.18
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Sequence
MAAAVAAAPGALGSLHAGGARLVAACSAWLCPGLRLPGSLAGRRAGPAIWAQGWVPAAGG
PAPKRGYSSEMKTEDELRVRHLEEENRGIVVLGINRAYGKNSLSKNLIKMLSKAVDALKS
DKKVRTIIIRSEVPGIFCAGADLKERAKMSSSEVGPFVSKIRAVINDIANLPVPTIAAID
GLALGGGLELALACDIRVAASSAKMGLVETKLAIIPGGGGTQRLPRAIGMSLAKELIFSA
RVLDGKEAKAVGLISHVLEQNQEGDAAYRKALDLAREFLPQGPVAMRVAKLAINQGMEVD
LVTGLAIEEACYAQTIPTKDRLEGLLAFKEKRPPRYKGE
Structure
1HZD ; 2ZQQ ; 2ZQR
Function Catalyzes the fifth step in the leucine degradation pathway, the reversible hydration of 3-methylglutaconyl-CoA (3-MG-CoA) to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) . Can catalyze the reverse reaction but at a much lower rate in vitro . HMG-CoA is then quickly degraded by another enzyme (such as HMG-CoA lyase) to give acetyl-CoA and acetoacetate . Uses other substrates such as (2E)-glutaconyl-CoA efficiently in vitro, and to a lesser extent 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA), crotonyl-CoA ((2E)-butenoyl-CoA) and 3-hydroxybutanoyl-CoA (the missing carboxylate reduces affinity to the active site) . Originally it was identified as an RNA-binding protein as it binds to AU-rich elements (AREs) in vitro . AREs direct rapid RNA degradation and mRNA deadenylation . Might have itaconyl-CoA hydratase activity, converting itaconyl-CoA into citramalyl-CoA in the C5-dicarboxylate catabolism pathway . The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, an antimicrobial metabolite and immunomodulator produced by macrophages during certain infections, that can act as a vitamin B12-poisoning metabolite .
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          1 Drugs
Sodium phenylbutyrate
 Drug Info Approved Muscular atrophy ICD11: 8B61 [1]
      Drugs in Phase 2 Clinical Trial Click to Show/Hide the Full List of Drugs:          1 Drugs
Phenylbutyrate
 Drug Info Phase 2 Phenylketonuria ICD11: 5C50 [1]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR005602 Phenylbutyryl-CoA PB:1-CoA Unclear - Unclear Sodium phenylbutyrate [1]
References
1 Identification of enzymes involved in oxidation of phenylbutyrate

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