6BML

Structure of human DHHC20 palmitoyltransferase, irreversibly inhibited by 2-bromopalmitate

PDB DOI: https://doi.org/10.2210/pdb6BML/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Komagataella pastoris
Mutation(s): No
Membrane Protein: Yes OPMPDBTMmpstruc

Deposited: 2017-11-15 Released: 2018-01-24
Deposition Author(s): Rana, M.S., Lee, C.-J., Banerjee, A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.95 Å
R-Value Free: 0.245
R-Value Work: 0.236
R-Value Observed: 0.237

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Fatty acyl recognition and transfer by an integral membraneS-acyltransferase.

Rana, M.S., Kumar, P., Lee, C.J., Verardi, R., Rajashankar, K.R., Banerjee, A.

(2018) Science 359

PubMed: 29326245 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1126/science.aao6326
Primary Citation of Related Structures:
6BML, 6BMM, 6BMN, 6BMS

PubMed 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.

Organizational Affiliation

Cell Biology and Neurobiology Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Macromolecule Content

Total Structure Weight: 70.67 kDa
Atom Count: 4,856
Modelled Residue Count: 586
Deposited Residue Count: 590
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
human DHHC20 palmitoyltransferase	A, B	295	Homo sapiens	Mutation(s): 0 Gene Names: ZDHHC20 EC: 2.3.1.225 (PDB Primary Data), 2.3.1 (UniProt) Membrane Entity: Yes
UniProt & NIH Common Fund Data Resources
Find proteins for Q5W0Z9 (Homo sapiens) Explore Q5W0Z9 Go to UniProtKB: Q5W0Z9
PHAROS: Q5W0Z9 GTEx: ENSG00000180776
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q5W0Z9
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
PAP Query on PAP Download Ideal Coordinates CCD File SDF format, chain J [auth B] MOL2 format, chain J [auth B] mmCIF format, chain J [auth B]	J [auth B]	3'-PHOSPHATE-ADENOSINE-5'-DIPHOSPHATE C₁₀ H₁₆ N₅ O₁₃ P₃ GBBWIZKLHXYJOA-KQYNXXCUSA-N		Interactions Focus chain J [auth B] Interactions & Density Focus chain J [auth B]
PLM Query on PLM Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain I [auth B] MOL2 format, chain E [auth A] MOL2 format, chain I [auth B] mmCIF format, chain E [auth A] mmCIF format, chain I [auth B]	E [auth A], I [auth B]	PALMITIC ACID C₁₆ H₃₂ O₂ IPCSVZSSVZVIGE-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain I [auth B] Interactions & Density Focus chain E [auth A] Focus chain I [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain K [auth B] MOL2 format, chain F [auth A] MOL2 format, chain K [auth B] mmCIF format, chain F [auth A] mmCIF format, chain K [auth B]	F [auth A], K [auth B]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain F [auth A] Focus chain K [auth B] Interactions & Density Focus chain F [auth A] Focus chain K [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain G [auth B] mmCIF format, chain H [auth B]	C [auth A], D [auth A], G [auth B], H [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain G [auth B] Focus chain H [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain G [auth B] Focus chain H [auth B]