5D40: Crystal Structure Of The 5-selective H176y Mutant Of Cytochrome Txte

The dynamic motions of protein structural elements, particularly flexible loops, are intimately linked with diverse aspects of enzyme catalysis. Engineering of these loop regions can alter protein stability, substrate binding and even dramatically impact enzyme function. When these flexible regions are unresolvable structurally, computational reconstruction in combination with large-scale molecular dynamics simulations can be used to guide the engineering strategy. Here we present a collaborative approach that consists of both experiment and computation and led to the discovery of a single mutation in the F/G loop of the nitrating cytochrome P450 TxtE that simultaneously controls loop dynamics and completely shifts the enzyme's regioselectivity from the C4 to the C5 position of L-tryptophan. Furthermore, we find that this loop mutation is naturally present in a subset of homologous nitrating P450s and confirm that these uncharacterized enzymes exclusively produce 5-nitro-L-tryptophan, a previously unknown biosynthetic intermediate.
PDB ID: 5D40Download
MMDB ID: 140216
PDB Deposition Date: 2015/8/6
Updated in MMDB: 2016/06
Experimental Method:
x-ray diffraction
Resolution: 1.51  Å
Source Organism:
Similar Structures:
Biological Unit for 5D40: monomeric; determined by author
Molecular Components in 5D40
Label Count Molecule
Protein (1 molecule)
P450-like Protein
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB