PDBsum entry 6tth

Cytosolic protein

PDB id: 6tth

Contents

Protein chains

410 a.a.

Ligands

FBP ×4

THR ×4

Waters ×192

PDB id:

6tth

Name:

Cytosolic protein

Title:

Pkm2 in complex with l-threonine

Structure:

Pyruvate kinase pkm. Chain: a, b, c, d. Synonym: cytosolic thyroid hormone-binding protein,cthbp,opa- interacting protein 3,oip-3,pyruvate kinase 2/3,pyruvate kinase muscle isozyme,thyroid hormone-binding protein 1,thbp1,tumor m2-pk, p58. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pkm, oip3, pk2, pk3, pkm2. Expressed in: escherichia coli. Expression_system_taxid: 562

Authors:

M.Saur,M.J.Hartshorn,J.Dong,J.Reeks,G.Bunkoczi,H.Jhoti,P.A.Williams

Key ref:

M.Saur et al. (2020). Fragment-based drug discovery using cryo-EM. Drug Discov Today, 25, 485-490. PubMed id: 31877353 DOI: 10.1016/j.drudis.2019.12.006

Date:

27-Dec-19 Release date: 15-Jan-20

Protein chains

P14618  (KPYM_HUMAN) -  Pyruvate kinase PKM from Homo sapiens

Seq: 531 a.a.

Struc: 410 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.1.40 - pyruvate kinase.
• Reaction: pyruvate + ATP = phosphoenolpyruvate + ADP + H⁺

pyruvate + ATP (Bound ligand (Het Group name = THR) matches with 55.56% similarity) = phosphoenolpyruvate + ADP + H(+) (Bound ligand (Het Group name = FBP) matches with 42.86% similarity)

• Enzyme class 3: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺
• Enzyme class 4: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.drudis.2019.12.006

Drug Discov Today 25:485-490 (2020)

PubMed id: 31877353

Fragment-based drug discovery using cryo-EM.

M.Saur, M.J.Hartshorn, J.Dong, J.Reeks, G.Bunkoczi, H.Jhoti, P.A.Williams.

ABSTRACT

Recent advances in electron cryo-microscopy (cryo-EM) structure determination have pushed the resolutions obtainable by the method into the range widely considered to be of utility for drug discovery. Here, we review the use of cryo-EM in fragment-based drug discovery (FBDD) based on in-house method development. We demonstrate not only that cryo-EM can reveal details of the molecular interactions between fragments and a protein, but also that the current reproducibility, quality, and throughput are compatible with FBDD. We exemplify this using the test system β-galactosidase (Bgal) and the oncology target pyruvate kinase 2 (PKM2).