PDBsum entry 3u2c

Oxidoreductase/oxidoreductase inhibitor

PDB id: 3u2c

Contents

Protein chain

315 a.a.

Ligands

NAP

PEG ×2

PG5 ×2

CIT

SUZ

PG4

Waters ×309

PDB id:

3u2c

Name:

Oxidoreductase/oxidoreductase inhibitor

Title:

Aldose reductase in complex with nsaid-type inhibitor at 1.0 a resolution

Structure:

Aldose reductase. Chain: a. Synonym: ar, aldehyde reductase, aldo-keto reductase family 1 member b1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: akr1b1, aldose reductase, aldr1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.00Å R-factor: 0.113 R-free: 0.138

Authors:

H.Steuber

Key ref:

H.Steuber (2011). An old NSAID revisited: crystal structure of aldose reductase in complex with sulindac at 1.0 Å supports a novel mechanism for its anticancer and antiproliferative effects. Chemmedchem, 6, 2155-2157. PubMed id: 21997888

Date:

03-Oct-11 Release date: 02-Nov-11

Protein chain

P15121  (ALDR_HUMAN) -  Aldo-keto reductase family 1 member B1 from Homo sapiens

Seq: 316 a.a.

Struc: 315 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.1.1.1.21 - aldose reductase.
• Reaction:
  1. an alditol + NAD⁺ = an aldose + NADH + H⁺
  2. an alditol + NADP⁺ = an aldose + NADPH + H⁺

alditol (Bound ligand (Het Group name = PEG) matches with 50.00% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = aldose + NADH + H(+)

alditol (Bound ligand (Het Group name = PEG) matches with 50.00% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = aldose + NADPH + H(+)

• Enzyme class 2: E.C.1.1.1.300 - NADP-retinol dehydrogenase.
• Reaction: all-trans-retinol + NADP⁺ = all-trans-retinal + NADPH + H⁺

all-trans-retinol (Bound ligand (Het Group name = SUZ) matches with 64.29% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = all-trans-retinal + NADPH + H(+)

• Enzyme class 3: E.C.1.1.1.372 - D/L-glyceraldehyde reductase.
• Reaction:
  1. glycerol + NADP⁺ = L-glyceraldehyde + NADPH + H⁺
  2. glycerol + NADP⁺ = D-glyceraldehyde + NADPH + H⁺

glycerol (Bound ligand (Het Group name = PEG) matches with 44.44% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = L-glyceraldehyde + NADPH + H(+)

glycerol (Bound ligand (Het Group name = PEG) matches with 44.44% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = D-glyceraldehyde + NADPH + H(+)

• Enzyme class 4: E.C.1.1.1.54 - allyl-alcohol dehydrogenase.
• Reaction: allyl alcohol + NADP⁺ = acrolein + NADPH + H⁺

allyl alcohol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = acrolein + NADPH + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

Chemmedchem 6:2155-2157 (2011)

PubMed id: 21997888

An old NSAID revisited: crystal structure of aldose reductase in complex with sulindac at 1.0 Å supports a novel mechanism for its anticancer and antiproliferative effects.

H.Steuber.

ABSTRACT

No abstract given.