Targeting KRAS(G12D) with Mutant-Selective Monobody Inhibitors

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NYU Dataset

Targeting KRAS(G12D) with Mutant-Selective Monobody Inhibitors

Part of: Koide Lab |

UID: 10635

Author(s): Padma Akkapeddi, Takamitsu Hattori, Imran Khan, Eliezra Glasser, Akiko Koide... See more...

Gayatri Ketavarapu, Michael Whaby, Mariyam Zuberic, Kai Wen Teng, Julia Lefler, Lorenzo Maso, Injin Bang, Michael C. Ostrowsk, John P. O’Bryan, Shohei Koide*

* Corresponding Author

Description: This study developed a series of synthetic binding proteins called monobodies that are selective to KRAS(G12D). KRAS(G12D) is a common mutation associated with deadly cancers, such as pancreatic and colorectal cancers. Although recent discoveries have revealed that KRAS(G12D) is no longer undruggable, there are still few direct inhibitors selective to KRAS(G12D). The dataset contains structural coordinates of monobody 12D1 and monobody 12D5 bound to KRAS(G12D). Due to the relative ease of generating these monobody inhibitors, this study suggests their utilization as therapeutic target in cancer.

Subject of Study

Subject Domain

Keywords

X-Ray Crystallography

Access

Restrictions: Free to All
Instructions: Structural coordinates data have been deposited in Protein Data Bank (PDB).; Access via PDB
Structural coordinate of monobody 12D1
Accession #: 8EZG

Access via PDB
Structural coordinate of monobody 12D5
Accession #: 8F0M

Associated Publications

Akkapeddi P, Hattori T, Khan I, Glasser E, Koide A, Ketavarapu G, Whaby M, Zuberi M, Teng KW, Lefler J, Maso L, Bang I, Ostrowski MC, O'Bryan JP, Koide S. Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors. Proc Natl Acad Sci U S A. 2023 Jul 11;120(28):e2302485120.

Data Type

Equipment Used

BD FACSVerse

Cytiva AKTA Pure

Illumina MiSeq System

Sartorius iQue

Sartorius Octet RED96e System

Superdex 75 10/300 GL

Zeiss LSM 710

Software Used

Coot

FlowJo

GraphPad Prism v9.0

ImageJ

Octet

Pairwise Structure Alignment

PDB-REDO

PDBePISA

Phaser

phenix.refine

Python

Grant Support: P30 CA016087/NCI NIH

R21 CA246457/NCI NIH

R01 CA212608/NCI NIH

R01 CA194864/NCI NIH

1I01BX002095/Department of Veterans Affairs

P30 CA138313/NCI NIH

F32 CA225131/NCI NIH

PF-18-180-01-TBE/American Cancer Society

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