PDBsum entry 1xpq

Oxidoreductase

PDB id: 1xpq

Contents

Protein chains

502 a.a. *

Ligands

SPM ×4

FAD ×4

Waters ×235

* Residue conservation analysis

PDB id:

1xpq

Name:

Oxidoreductase

Title:

Crystal structure of fms1, a polyamine oxidase from yeast

Structure:

Polyamine oxidase fms1. Chain: a, b, c, d. Synonym: fenpropimorph resistance multicopy suppressor 1. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: fms1, ymr020w, ym9711.09. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.51Å R-factor: 0.202 R-free: 0.276

Authors:

Q.Huang,Q.Liu,Q.Hao

Key ref:

Q.Huang et al. (2005). Crystal structures of Fms1 and its complex with spermine reveal substrate specificity. J Mol Biol, 348, 951-959. PubMed id: 15843025 DOI: 10.1016/j.jmb.2005.03.008

Date:

09-Oct-04 Release date: 26-Apr-05

Protein chains

P50264  (FMS1_YEAST) -  Polyamine oxidase FMS1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 508 a.a.

Struc: 502 a.a.

Enzyme reactions

• Enzyme class: E.C.1.5.3.17 - non-specific polyamine oxidase.
• Reaction:
  1. spermine + O2 + H2O = 3-aminopropanal + spermidine + H2O2
  2. spermidine + O2 + H2O = 3-aminopropanal + putrescine + H2O2
  3. N₁-acetylspermine + O2 + H2O = 3-acetamidopropanal + spermidine + H2O2
  4. N₁-acetylspermidine + O2 + H2O = 3-acetamidopropanal + putrescine + H2O2

spermine (Bound ligand (Het Group name = SPM) corresponds exactly) + O2 + H2O = 3-aminopropanal + spermidine + H2O2

spermidine (Bound ligand (Het Group name = SPM) matches with 71.43% similarity) + O2 + H2O = 3-aminopropanal + putrescine + H2O2

N(1)-acetylspermine + O2 + H2O = 3-acetamidopropanal (Bound ligand (Het Group name = SPM) matches with 71.43% similarity) + spermidine + H2O2

N(1)-acetylspermidine + O2 + H2O = 3-acetamidopropanal (Bound ligand (Het Group name = SPM) matches with 42.86% similarity) + putrescine + H2O2

• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) corresponds exactly)

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

reference

DOI no: 10.1016/j.jmb.2005.03.008

J Mol Biol 348:951-959 (2005)

PubMed id: 15843025

Crystal structures of Fms1 and its complex with spermine reveal substrate specificity.

Q.Huang, Q.Liu, Q.Hao.

ABSTRACT

Fms1 is a rate-limiting enzyme for the biosynthesis of pantothenic acid in yeast. Fms1 has polyamine oxidase (PAO) activity, which converts spermine into spermidine and 3-aminopropanal. The 3-aminopropanal is further oxidized to produce beta-alanine, which is necessary for the biosynthesis of pantothenic acid. The crystal structures of Fms1 and its complex with the substrate spermine have been determined using the single-wavelength anomalous diffraction (SAD) phasing method. Fms1 consists of an FAD-binding domain, with Rossmann fold topology, and a substrate-binding domain. The active site is a tunnel located at the interface of the two domains. The substrate spermine binds to the active site mainly via hydrogen bonds and hydrophobic interactions. In the complex, C11 but not C9 of spermine is close enough to the catalytic site (N5 of FAD) to be oxidized. Therefore, the products are spermidine and 3-aminopropanal, rather than 3-(aminopropyl) 4-aminobutyraldehyde and 1,3-diaminoprone.

Selected figure(s)

Figure 3.
Figure 3. (a) The F[o]-F[c] omit map contoured at 4s showing spermine in the complex. (b) In the complex, the substrate spermine binds to the active site of the enzyme mainly through two hydrogen bonds and hydrophobic interactions, especially the W174-spermine (C6-C9)-W65 hydrophobic sandwich. The C11 atom is close enough (3.76 Å) to the N5 atom of FAD to be oxidized, while C9 is too far from N5 of FAD to be oxidized. (c) A LIGPLOT42 outlining the substrate-tunnel interactions.

Figure 4.
Figure 4. The binding of the substrate spermine to the active site of Fms1 induces conformation changes of the protein. The side-chain of W174 (native in green; complex in red) moves to a new position to form the W174-spermine-W65 hydrophobic sandwich.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 348, 951-959) copyright 2005.

Figures were selected by an automated process.