6SBV

X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)

Summary for 6SBV

• Entry DOI: 10.2210/pdb6sbv/pdb
• Related: 6SBU
• Descriptor: L-lactate dehydrogenase A chain, ~{N}-[3-[(7-nitrodibenzofuran-2-yl)sulfonylamino]phenyl]-1-oxidanyl-cyclopropane-1-carboxamide (3 entities in total)
• Functional Keywords: ldha, oxidoreductase, oxidoreductase inhibitor, allosteric inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 8
• Total formula weight: 297023.82

Authors

Friberg, A.,Puetter, V.,Nguyen, D.,Rehwinkel, H. (deposition date: 2019-07-22, release date: 2020-06-10, Last modification date: 2024-01-24)

Primary citation

Friberg, A.,Rehwinkel, H.,Nguyen, D.,Putter, V.,Quanz, M.,Weiske, J.,Eberspacher, U.,Heisler, I.,Langer, G.
Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A.
Acs Omega, 5:13034-13041, 2020

PubMed Abstract: Lactate dehydrogenase A (LDHA) is frequently overexpressed in tumors, thereby sustaining high glycolysis rates, tumor growth, and chemoresistance. High-throughput screening resulted in the identification of phthalimide and dibenzofuran derivatives as novel lactate dehydrogenase inhibitors, selectively inhibiting the activity of the LDHA isoenzyme. Cocrystallization experiments confirmed target engagement in addition to demonstrating binding to a novel allosteric binding site present in all four LDHA subunits of the LDH5 homotetramer.

PubMed: 32548488
DOI: 10.1021/acsomega.0c00715

Experimental method

X-RAY DIFFRACTION (2.6 Å)