4XX1: Low Resolution Structure Of Lcat In Complex With Fab1

Citation:
Abstract
LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. Here we report the 2.65 A crystal structure of the human LCAT protein. Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. The crystal structure reveals that LCAT has an alpha/beta hydrolase core with two additional subdomains that play important roles in LCAT function. Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity.
PDB ID: 4XX1Download
MMDB ID: 131288
PDB Deposition Date: 2015/1/29
Updated in MMDB: 2015/09
Experimental Method:
x-ray diffraction
Resolution: 3.6  Å
Similar Structures:
Biological Unit for 4XX1: trimeric; determined by author and by software (PISA)
Molecular Components in 4XX1
Label Count Molecule
Proteins (3 molecules)
1
Fab1 Light Chain
Molecule annotation
1
Fab1 Heavy Chain
Molecule annotation
1
Phosphatidylcholine-sterol Acyltransferase(Gene symbol: LCAT)
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

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