4XX1

Low resolution structure of LCAT in complex with Fab1

Summary for 4XX1

• Entry DOI: 10.2210/pdb4xx1/pdb
• Related: 4XWG
• Descriptor: Fab1 light chain, Fab1 heavy chain, Phosphatidylcholine-sterol acyltransferase, ... (4 entities in total)
• Functional Keywords: a/b hydrolase, complex, hydrolase-immune system complex, hydrolase/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 9
• Total formula weight: 290927.53

Authors

Piper, D.E.,Walker, N.P.C.,Romanow, W.G.,Thibault, S.T. (deposition date: 2015-01-29, release date: 2015-07-29, Last modification date: 2023-09-27)

Primary citation

Piper, D.E.,Romanow, W.G.,Gunawardane, R.N.,Fordstrom, P.,Masterman, S.,Pan, O.,Thibault, S.T.,Zhang, R.,Meininger, D.,Schwarz, M.,Wang, Z.,King, C.,Zhou, M.,Walker, N.P.
The high-resolution crystal structure of human LCAT.
J.Lipid Res., 56:1711-1719, 2015

PubMed 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 Å 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 α/β 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.

PubMed: 26195816
DOI: 10.1194/jlr.M059873

Experimental method

X-RAY DIFFRACTION (3.6 Å)