Cryogenic human alkaline ceramidase 3 (ACER3) at 2.6 A resolution determined by Serial Crystallography (SSX) using CrystalDirectCryogenic human alkaline ceramidase 3 (ACER3) at 2.6 A resolution determined by Serial Crystallography (SSX) using CrystalDirect

Structural highlights

6yxh is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ACER3_HUMAN Alkaline ceramidase 3 deficiency.

Function

ACER3_HUMAN Hydrolyzes only phytoceramide into phytosphingosine and free fatty acid. Does not have reverse activity.

Publication Abstract from PubMed

Membrane proteins are central to many pathophysiological processes, yet remain very difficult to analyze structurally. Moreover, high-throughput structure-based drug discovery has not yet been exploited for membrane proteins because of lack of automation. Here, we present a facile and versatile platform for in meso membrane protein crystallization, enabling rapid atomic structure determination at both cryogenic and room temperatures. We apply this approach to human integral membrane proteins, which allowed us to identify different conformational states of intramembrane enzyme-product complexes and analyze by molecular dynamics simulations the structural dynamics of the ADIPOR2 integral membrane protein. Finally, we demonstrate an automated pipeline combining high-throughput microcrystal soaking, automated laser-based harvesting, and serial crystallography, enabling screening of small-molecule libraries with membrane protein crystals grown in meso. This approach brings needed automation to this important class of drug targets and enables high-throughput structure-based ligand discovery with membrane proteins.

An automated platform for structural analysis of membrane proteins through serial crystallography.,Healey RD, Basu S, Humm AS, Leyrat C, Cong X, Golebiowski J, Dupeux F, Pica A, Granier S, Marquez JA Cell Rep Methods. 2021 Oct 25;1(6):None. doi: 10.1016/j.crmeth.2021.100102. PMID:34723237[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Healey RD, Basu S, Humm AS, Leyrat C, Cong X, Golebiowski J, Dupeux F, Pica A, Granier S, Marquez JA. An automated platform for structural analysis of membrane proteins through serial crystallography. Cell Rep Methods. 2021 Oct 25;1(6):None. doi: 10.1016/j.crmeth.2021.100102. PMID:34723237 doi:http://dx.doi.org/10.1016/j.crmeth.2021.100102

6yxh, resolution 2.60Å

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