PUBLICATION
Fatty acyl recognition and transfer by an integral membrane S-acyltransferase.
- Authors
- Rana, M.S., Kumar, P., Lee, C.J., Verardi, R., Rajashankar, K.R., Banerjee, A.
- ID
- ZDB-PUB-180208-1
- Date
- 2018
- Source
- Science (New York, N.Y.) 359(6372): (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Acyl Coenzyme A/metabolism*
- Acyltransferases/chemistry*
- Acyltransferases/genetics
- Acyltransferases/metabolism
- Animals
- Catalytic Domain
- Crystallization
- Crystallography, X-Ray
- Cysteine/chemistry
- Humans
- Lipoylation
- Models, Molecular
- Mutation
- Protein Domains
- Protein Structure, Secondary
- Substrate Specificity
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 29326245 Full text @ Science
Citation
Rana, M.S., Kumar, P., Lee, C.J., Verardi, R., Rajashankar, K.R., Banerjee, A. (2018) Fatty acyl recognition and transfer by an integral membrane S-acyltransferase.. Science (New York, N.Y.). 359(6372).
Abstract
DHHC (Asp-His-His-Cys) palmitoyltransferases are eukaryotic integral membrane enzymes that catalyze protein palmitoylation, which is important in a range of physiological processes, including small guanosine triphosphatase (GTPase) signaling, cell adhesion, and neuronal receptor scaffolding. We present crystal structures of two DHHC palmitoyltransferases and a covalent intermediate mimic. The active site resides at the membrane-cytosol interface, which allows the enzyme to catalyze thioester-exchange chemistry by using fatty acyl-coenzyme A and explains why membrane-proximal cysteines are candidates for palmitoylation. The acyl chain binds in a cavity formed by the transmembrane domain. We propose a mechanism for acyl chain-length selectivity in DHHC enzymes on the basis of cavity mutants with preferences for shorter and longer acyl chains.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping