3DZ5: Human Adometdc With Covalently Bound 5'-[(2-aminooxyethyl) Methylamino]-5'-deoxy-8-methyladenosine

Citation:
Abstract
S-adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C(8)-substituted adenine analogues bound in the active site.
PDB ID: 3DZ5Download
MMDB ID: 70111
PDB Deposition Date: 2008/7/29
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.43  Å
Source Organism:
Similar Structures:
Biological Unit for 3DZ5: dimeric; determined by author and by software (PISA)
Molecular Components in 3DZ5
Label Count Molecule
Proteins (2 molecules)
1
S-adenosylmethionine Decarboxylase Beta Chain(Gene symbol: AMD1)
Molecule annotation
1
S-adenosylmethionine Decarboxylase Alpha Chain(Gene symbol: AMD1)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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