PDBsum entry 6w3f

Biosynthetic protein

PDB id: 6w3f

Contents

Protein chains

115 a.a.

Waters ×55

PDB id:

6w3f

Name:

Biosynthetic protein

Title:

Rd1ntf2_05_i64f_a80g_t94p_d101k_l106w

Structure:

Rd1ntf2_05_i64f_a80g_t94p_d101k_l106w. Chain: a, b. Engineered: yes

Source:

Synthetic construct. Organism_taxid: 32630. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.83Å R-factor: 0.220 R-free: 0.255

Authors:

M.J.Bick,B.Basanta,B.Sankaran,D.Baker

Key ref:

B.Basanta et al. (2020). An enumerative algorithm for de novo design of proteins with diverse pocket structures. Proc Natl Acad Sci U S A, 117, 22135-22145. PubMed id: 32839327 DOI: 10.1073/pnas.2005412117

Date:

09-Mar-20 Release date: 15-Apr-20

Protein chains

No UniProt id for this chain

Struc: 115 a.a.

DOI no: 10.1073/pnas.2005412117

Proc Natl Acad Sci U S A 117:22135-22145 (2020)

PubMed id: 32839327

An enumerative algorithm for de novo design of proteins with diverse pocket structures.

B.Basanta, M.J.Bick, A.K.Bera, C.Norn, C.M.Chow, L.P.Carter, I.Goreshnik, F.Dimaio, D.Baker.

ABSTRACT

To create new enzymes and biosensors from scratch, precise control over the structure of small-molecule binding sites is of paramount importance, but systematically designing arbitrary protein pocket shapes and sizes remains an outstanding challenge. Using the NTF2-like structural superfamily as a model system, we developed an enumerative algorithm for creating a virtually unlimited number of de novo proteins supporting diverse pocket structures. The enumerative algorithm was tested and refined through feedback from two rounds of large-scale experimental testing, involving in total the assembly of synthetic genes encoding 7,896 designs and assessment of their stability on yeast cell surface, detailed biophysical characterization of 64 designs, and crystal structures of 5 designs. The refined algorithm generates proteins that remain folded at high temperatures and exhibit more pocket diversity than naturally occurring NTF2-like proteins. We expect this approach to transform the design of small-molecule sensors and enzymes by enabling the creation of binding and active site geometries much more optimal for specific design challenges than is accessible by repurposing the limited number of naturally occurring NTF2-like proteins.