4YVF

Structure of S-adenosyl-L-homocysteine hydrolase

Summary for 4YVF

• Entry DOI: 10.2210/pdb4yvf/pdb
• Descriptor: Adenosylhomocysteinase, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, 2-{[5-chloro-2-(4-chlorophenoxy)phenyl](2-{[2-(methylamino)ethyl]amino}-2-oxoethyl)amino}-N-(1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide, ... (4 entities in total)
• Functional Keywords: sahh, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 97989.76

Authors

Akiko, K. (deposition date: 2015-03-20, release date: 2015-11-25, Last modification date: 2024-03-20)

Primary citation

Nakao, A.,Suzuki, H.,Ueno, H.,Iwasaki, H.,Setsuta, T.,Kashima, A.,Sunada, S.
Discovery and structural analyses of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs.
Bioorg.Med.Chem., 23:4952-4969, 2015

PubMed Abstract: Optimization of a new series of S-adenosyl-L-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 ± 3, 5.0 ± 2.0, and 8.5 ± 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD(+) and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction.

PubMed: 26037610
DOI: 10.1016/j.bmc.2015.05.018

Experimental method

X-RAY DIFFRACTION (2.7 Å)