5MHH

Crystal structure of engineered human lipocalin 2 carrying p-boronophenylalanine at position 36

Summary for 5MHH

• Entry DOI: 10.2210/pdb5mhh/pdb
• Descriptor: Neutrophil gelatinase-associated lipocalin, SULFATE ION (3 entities in total)
• Functional Keywords: beta-barrel, p-boronophenylalanine, lipocalin, strep-tag, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 22158.73

Authors

Skerra, A.,Eichinger, A. (deposition date: 2016-11-24, release date: 2017-10-11, Last modification date: 2024-10-16)

Primary citation

Edwardraja, S.,Eichinger, A.,Theobald, I.,Sommer, C.A.,Reichert, A.J.,Skerra, A.
Rational Design of an Anticalin-Type Sugar-Binding Protein Using a Genetically Encoded Boronate Side Chain.
ACS Synth Biol, 6:2241-2247, 2017

PubMed Abstract: The molecular recognition of carbohydrates plays a fundamental role in many biological processes. However, the development of carbohydrate-binding reagents for biomedical research and use poses a challenge due to the generally poor affinity of proteins toward sugars in aqueous solution. Here, we describe the effective molecular recognition of pyranose monosaccharides (in particular, galactose and mannose) by a rationally designed protein receptor based on the human lipocalin scaffold (Anticalin). Complexation relies on reversible covalent cis-diol boronate diester formation with a genetically encoded l-boronophenylalanine (Bpa) residue which was incorporated as a non-natural amino acid at a sterically permissive position in the ligand pocket of the Anticalin, as confirmed by X-ray crystallography. Compared with the metal-ion and/or avidity-dependent oligovalent lectins that prevail in nature, our approach offers a novel and promising route to generate tight sugar-binding reagents both as research reagents and for biomedical applications.

PubMed: 28937743
DOI: 10.1021/acssynbio.7b00199

Experimental method

X-RAY DIFFRACTION (2 Å)