5JC6

Carboxypeptidase B with 2-nd zinc and acetate ion

Summary for 5JC6

• Entry DOI: 10.2210/pdb5jc6/pdb
• Descriptor: Carboxypeptidase B, ZINC ION, ACETATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase
• Biological source: Sus scrofa (Pig)
• Total number of polymer chains: 1
• Total formula weight: 34923.75

Authors

Timofeev, V.I.,Akparov, V.K.,Kuranova, I.P. (deposition date: 2016-04-14, release date: 2017-05-24, Last modification date: 2024-10-23)

Primary citation

Akparov, V.,Timofeev, V.,Khaliullin, I.,Svedas, V.,Kuranova, I.
Structure of the carboxypeptidase B complex with N-sulfamoyl-L-phenylalanine - a transition state analog of non-specific substrate.
J. Biomol. Struct. Dyn., 36:956-965, 2018

PubMed Abstract: Carboxypeptidase B (EC 3.4.17.2) (CPB) is commonly used in the industrial insulin production and as a template for drug design. However, its ability to discriminate substrates with hydrophobic, hydrophilic, and charged side chains is not well understood. We report structure of CPB complex with a transition state analog N-sulfamoyl-L-phenylalanine solved at 1.74Å. The study provided an insight into structural basis of CPB substrate specificity. Ligand binding is affected by structure-depended conformational changes of Asp255 in S1'-subsite, interactions with Asn144 and Arg145 in C-terminal binding subsite, and Glu270 in the catalytic center. Side chain of the non-specific substrate analog SPhe in comparison with that of specific substrate analog SArg (reported earlier) not only loses favorable electrostatic interactions and two hydrogen bonds with Asp255 and three fixed water molecules, but is forced to be in the unfavorable hydrophilic environment. Thus, Ser207, Gly253, Tyr248, and Asp255 residues play major role in the substrate recognition by S1'-subsite.

PubMed: 28274181
DOI: 10.1080/07391102.2017.1304242

Experimental method

X-RAY DIFFRACTION (1.4 Å)