PDBsum entry: 1pz0

Oxidoreductase

PDB id: 1pz0

Contents

Protein chain

311 a.a. *

Ligands

NAP

Metals

_NA

Waters ×210

* Residue conservation analysis

PDB id:

1pz0

Name:

Oxidoreductase

Title:

Structure of NADPH-dependent family 11 aldo-keto reductase akr11a(holo)

Structure:

Iols protein. Chain: a. Synonym: vegetative protein 147, veg147. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 1423. Gene: iols or ss92er. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.35Å R-factor: 0.189 R-free: 0.256

Authors:

A.H.Ehrensberger,D.K.Wilson

Key ref:

A.H.Ehrensberger and D.K.Wilson (2004). Structural and catalytic diversity in the two family 11 aldo-keto reductases. J Mol Biol, 337, 661-673. PubMed id: 15019785 DOI: 10.1016/j.jmb.2004.01.059

Date:

09-Jul-03 Release date: 30-Mar-04

Protein chain

P46336  (IOLS_BACSU) -  Protein IolS

Seq: 310 a.a.

Struc: 311 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: oxidation reduction (1 term)
• Biochemical function: oxidoreductase activity (1 term)

DOI no: 10.1016/j.jmb.2004.01.059

J Mol Biol 337:661-673 (2004)

PubMed id: 15019785

Structural and catalytic diversity in the two family 11 aldo-keto reductases.

A.H.Ehrensberger, D.K.Wilson.

ABSTRACT

Aldo-keto reductases (AKRs) are a large superfamily of NAD(P)H-dependent enzymes that function in a wide range of biological processes. The structures of two enzymes from the previously uncharacterized family 11 (AKR11A and AKR11B), the products of the iolS and yhdN genes of Bacillus subtilis have been determined. AKR11B appears to be a relatively conventional member of the superfamily with respect to structural and biochemical properties. It is an efficient enzyme, specific for NADPH and possesses a catalytic triad typical for AKRs. AKR11A exhibits catalytic divergence from the other members of the superfamily and, surprisingly, AKR11B, the most closely related aldo-keto reductase in sequence. Although both have conserved catalytic residues consisting of an acidic tyrosine, a lysine and an aspartate, a water molecule interrupts this triad in cofactor-bound AKR11A by inserting between the lysine and tyrosine side-chains. This results in a unique architecture for an AKR active site with scant catalytic power. In addition, the absence of a bulky tryptophan side-chain in AKR11A allows an unconventional conformation of the bound NADP+ cosubstrate, raising the possibility that it donates the 4-pro-S hydride rather than the 4-pro-R hydride seen in most other AKRs. Based upon the architecture of the active site and the resulting reaction velocities, it therefore appears that functioning as an efficient oxido-reductase is probably not the primary role of AKR11A. A comparison of the apo and holo forms of AKR11A demonstrates that the cosubstrate does not play the dramatic role in active site assembly seen in other superfamily members.

Selected figure(s)

Figure 1.
Figure 1. Stereo views of C^a traces of the holo forms of (a) AKR11A and (b) AKR11B. Also included are ball and stick representations of the NADP+ cosubstrates. Note that loop 7, also referred to as the safety belt, is in an open conformation in AKR11A and a closed conformation in AKR11B. Figures 1-5 were generated using the programs MOLSCRIPT,[45.] BOBSCRIPT [46.] and Raster3D. [47.]

Figure 2.
Figure 2. Interactions between loops 1 and 7 in AKR11B form the closed safety belt, which in AKRs is known to lock on top of the NADP+ when this binds. Hydrogen bonds between amino acid residues D224-G29, D225-W28 and L226-M27 are shown in yellow. These are complemented by hydrophobic interactions between L226 and residues W21 and W28. NADP+ is colored in grey.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 337, 661-673) copyright 2004.

Figures were selected by an automated process.