Unknown

Dataset Information

0

Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes.


ABSTRACT: 'Radical SAM' enzymes generate catalytic radicals by combining a 4Fe-4S cluster and S-adenosylmethionine (SAM) in close proximity. We present the first crystal structure of a Radical SAM enzyme, that of HemN, the Escherichia coli oxygen-independent coproporphyrinogen III oxidase, at 2.07 A resolution. HemN catalyzes the essential conversion of coproporphyrinogen III to protoporphyrinogen IX during heme biosynthesis. HemN binds a 4Fe-4S cluster through three cysteine residues conserved in all Radical SAM enzymes. A juxtaposed SAM coordinates the fourth Fe ion through its amide nitrogen and carboxylate oxygen. The SAM sulfonium sulfur is near both the Fe (3.5 A) and a neighboring sulfur of the cluster (3.6 A), allowing single electron transfer from the 4Fe-4S cluster to the SAM sulfonium. SAM is cleaved yielding a highly oxidizing 5'-deoxyadenosyl radical. HemN, strikingly, binds a second SAM immediately adjacent to the first. It may thus successively catalyze two propionate decarboxylations. The structure of HemN reveals the cofactor geometry required for Radical SAM catalysis and sets the stage for the development of inhibitors with antibacterial function due to the uniquely bacterial occurrence of the enzyme.

SUBMITTER: Layer G 

PROVIDER: S-EPMC291839 | biostudies-literature | 2003 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes.

Layer Gunhild G   Moser Jürgen J   Heinz Dirk W DW   Jahn Dieter D   Schubert Wolf-Dieter WD  

The EMBO journal 20031201 23


'Radical SAM' enzymes generate catalytic radicals by combining a 4Fe-4S cluster and S-adenosylmethionine (SAM) in close proximity. We present the first crystal structure of a Radical SAM enzyme, that of HemN, the Escherichia coli oxygen-independent coproporphyrinogen III oxidase, at 2.07 A resolution. HemN catalyzes the essential conversion of coproporphyrinogen III to protoporphyrinogen IX during heme biosynthesis. HemN binds a 4Fe-4S cluster through three cysteine residues conserved in all Rad  ...[more]

Similar Datasets

| S-EPMC10965808 | biostudies-literature
| S-EPMC7813823 | biostudies-literature
| S-EPMC4012327 | biostudies-literature
| S-EPMC2996862 | biostudies-literature
| S-EPMC9526504 | biostudies-literature
| S-EPMC4139163 | biostudies-literature
| S-EPMC2515868 | biostudies-literature
| S-EPMC7227399 | biostudies-literature
| S-EPMC1186208 | biostudies-other
| S-EPMC8837180 | biostudies-literature