4L6C
Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the inhibitor pib-t
Summary for 4L6C
| Entry DOI | 10.2210/pdb4l6c/pdb |
| Related | 4L6A |
| Descriptor | 5'(3')-deoxyribonucleotidase, mitochondrial, MAGNESIUM ION, PHOSPHATE ION, ... (7 entities in total) |
| Functional Keywords | 5'-nucleotidase, mitochondria, protein conformation, sequence homology, had-like, hydrolase, dephosphorylation, phosphorylation, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Mitochondrion: Q9NPB1 |
| Total number of polymer chains | 1 |
| Total formula weight | 24695.81 |
| Authors | Pachl, P.,Brynda, J.,Rezacova, P. (deposition date: 2013-06-12, release date: 2014-09-10, Last modification date: 2024-02-28) |
| Primary citation | Simak, O.,Pachl, P.,Fabry, M.,Budesinsky, M.,Jandusik, T.,Hnizda, A.,Sklenickova, R.,Petrova, M.,Veverka, V.,Rezacova, P.,Brynda, J.,Rosenberg, I. Conformationally constrained nucleoside phosphonic acids - potent inhibitors of human mitochondrial and cytosolic 5'(3')-nucleotidases. Org.Biomol.Chem., 12:7971-7982, 2014 Cited by PubMed Abstract: This work describes novel in vitro inhibitors of human mitochondrial (mdN) and cytosolic (cdN) 5'(3')-deoxynucleotidases. We designed a series of derivatives of the lead compound (S)-1-[2-deoxy-3,5-O-(phosphonobenzylidene)-β-d-threo-pentofuranosyl]thymine bearing various substituents in the para position of the benzylidene moiety. Detailed kinetic study revealed that certain para substituents increase the inhibitory potency (iodo derivative; K = 2.71 μM) and some induce a shift in selectivity toward cdN (carboxy derivative, K = 11.60 μM; iodoxy derivative, K = 6.60 μM). Crystal structures of mdN in complex with three of these compounds revealed that various para substituents lead to two alternative inhibitor binding modes within the enzyme active site. Two binding modes were also identified for cdN complexes by heteronuclear NMR spectroscopy. PubMed: 25178098DOI: 10.1039/c4ob01332h PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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