PDBsum entry 4g1b

Oxidoreductase

PDB id: 4g1b

Contents

Protein chains

398 a.a.

Ligands

HEM ×4

FAD ×4

ECN ×4

Waters ×106

PDB id:

4g1b

Name:

Oxidoreductase

Title:

X-ray structure of yeast flavohemoglobin in complex with econazole

Structure:

Flavohemoglobin. Chain: a, b, c, d. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 307796. Strain: yjm789. Gene: yhb1, scy_2125. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

3.00Å R-factor: 0.232 R-free: 0.280

Authors:

E.El Hammi,E.Warkentin,U.Demmer,L.Baciou,U.Ermler

Key ref:

E.El Hammi et al. (2012). Active site analysis of yeast flavohemoglobin based on its structure with a small ligand or econazole. Febs J, 279, 4565-4575. PubMed id: 23095020

Date:

10-Jul-12 Release date: 14-Nov-12

Protein chains

A6ZUP2  (A6ZUP2_YEAS7) -  nitric oxide dioxygenase from Saccharomyces cerevisiae (strain YJM789)

Seq: 399 a.a.

Struc: 398 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.12.17 - nitric oxide dioxygenase.
• Reaction:
  1. 2 nitric oxide + NADPH + 2 O2 = 2 nitrate + NADP⁺ + H⁺
  2. 2 nitric oxide + NADH + 2 O2 = 2 nitrate + NAD⁺ + H⁺
• Cofactor: FAD; Heme

FAD (Bound ligand (Het Group name = FAD) corresponds exactly) Heme (Bound ligand (Het Group name = HEM) matches with 95.45% similarity)

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

reference

Febs J 279:4565-4575 (2012)

PubMed id: 23095020

Active site analysis of yeast flavohemoglobin based on its structure with a small ligand or econazole.

E.El Hammi, E.Warkentin, U.Demmer, N.M.Marzouki, U.Ermler, L.Baciou.

ABSTRACT

Flavohemoglobins (flavoHbs) serve various microorganisms as the major protective enzymes against NO˙-mediated toxicity. FlavoHbs dominantly function as an NO˙ dioxygenase (O2+ NO→ NO3 -), the required electron being shuttled from NAD(P)H via FAD to the heme iron. The X-ray structures of the flavoHb from Saccharomyces cerevisae presented in complex with an unknown small ligand (Yhb) and with econazole (Yhb(E) ) at 2.1 and 3.0 Å resolutions, respectively, reveal a high architectural accordance between prokaryotic and eukaryotic family members. The active site is characterized by a proximal heme side with a strictly conserved histidine, glutamate and tyrosine triad and a highly variable distal heme side with helix shifts up to 10 Å mainly dependent on the presence/absence and size of the bound ligand. In yeast flavoHb, the small heme iron ligand adjusts a catalytically productive active site geometry that reliably suggests the NO and O(2) binding site. O(2) is activated by its ligation to an electron-rich heme iron and a hydrogen bond to Tyr29 and Gln53. High active site similarities between eukaryotic Yhb and bacterial single-domain globins argue for identical biochemical reactions. Binding of the bulky econazole implies a large-scale induced-fit process concerning, in particular, an outwards shift of helices B and E to increase the active site pocket. Yeast Yhb and Ralstonia eutropha flavoHb both structurally studied in complex with econazole indicate conformational differences between the inhibitors and the polypeptide primarily caused by stable binding of a phospholipid to the latter and by distinct loop D structures. DATABASE: Structural data and final coordinates of Yhb and Yhb-econazole are available in the Protein Data Bank under the accession numbers 4G1V and 4G1B.