PDBsum entry 5eeh

Transferase

PDB id: 5eeh

Contents

Protein chains

342 a.a.

Ligands

SAH ×3

P9P ×15

SO4 ×9

Waters ×913

PDB id:

5eeh

Name:

Transferase

Title:

Crystal structure of carminomycin-4-o-methyltransferase dnrk in complex with sah and 2-chloro-4-nitrophenol

Structure:

Carminomycin 4-o-methyltransferase dnrk. Chain: a, b, c. Synonym: comt,anthracycline 4-o-methyltransferase. Engineered: yes

Source:

Streptomyces peucetius. Organism_taxid: 1950. Gene: dnrk. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

1.82Å R-factor: 0.155 R-free: 0.186

Authors:

F.Wang,S.Singh,J.S.Thorson,G.N.Phillips Jr.,Enzyme Discovery For Natural Product Biosynthesis (Natpro)

Key ref:

T.D.Huber et al. (2016). Functional AdoMet Isosteres Resistant to Classical AdoMet Degradation Pathways. Acs Chem Biol, 11, 2484-2491. PubMed id: 27351335 DOI: 10.1021/acschembio.6b00348

Date:

22-Oct-15 Release date: 16-Dec-15

Protein chains

Q06528  (DNRK_STRPE) -  Carminomycin 4-O-methyltransferase DnrK from Streptomyces peucetius

Seq: 356 a.a.

Struc: 342 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.292 - carminomycin 4-O-methyltransferase.
• Reaction: carminomycin + S-adenosyl-L-methionine = daunorubicin + S-adenosyl-L- homocysteine + H⁺

carminomycin + S-adenosyl-L-methionine = daunorubicin + S-adenosyl-L- homocysteine + H(+) (Bound ligand (Het Group name = SAH) corresponds exactly)

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

reference

DOI no: 10.1021/acschembio.6b00348

Acs Chem Biol 11:2484-2491 (2016)

PubMed id: 27351335

Functional AdoMet Isosteres Resistant to Classical AdoMet Degradation Pathways.

T.D.Huber, F.Wang, S.Singh, B.R.Johnson, J.Zhang, M.Sunkara, S.G.Van Lanen, A.J.Morris, G.N.Phillips, J.S.Thorson.

ABSTRACT

S-adenosyl-l-methionine (AdoMet) is an essential enzyme cosubstrate in fundamental biology with an expanding range of biocatalytic and therapeutic applications. We report the design, synthesis, and evaluation of stable, functional AdoMet isosteres that are resistant to the primary contributors to AdoMet degradation (depurination, intramolecular cyclization, and sulfonium epimerization). Corresponding biochemical and structural studies demonstrate the AdoMet surrogates to serve as competent enzyme cosubstrates and to bind a prototypical class I model methyltransferase (DnrK) in a manner nearly identical to AdoMet. Given this conservation in function and molecular recognition, the isosteres presented are anticipated to serve as useful surrogates in other AdoMet-dependent processes and may also be resistant to, and/or potentially even inhibit, other therapeutically relevant AdoMet-dependent metabolic transformations (such as the validated drug target AdoMet decarboxylase). This work also highlights the ability of the prototypical class I model methyltransferase DnrK to accept non-native surrogate acceptors as an enabling feature of a new high-throughput methyltransferase assay.