PDBsum entry 3m4h

Oxidoreductase/oxidoreductase inhibitor

PDB id: 3m4h

Contents

Protein chain

316 a.a. *

Ligands

NAP

388

CIT

Metals

_BR

Waters ×412

* Residue conservation analysis

PDB id:

3m4h

Name:

Oxidoreductase/oxidoreductase inhibitor

Title:

Human aldose reductase mutant t113v complexed with idd388

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: alr2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

0.94Å R-factor: 0.103 R-free: 0.122

Authors:

C.Koch,A.Heine,G.Klebe

Key ref:

C.Koch et al. (2011). Tracing the detail: how mutations affect binding modes and thermodynamic signatures of closely related aldose reductase inhibitors. J Mol Biol, 406, 700-712. PubMed id: 21185307

Date:

11-Mar-10 Release date: 15-Dec-10

Protein chain

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

Seq: 316 a.a.

Struc: 316 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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

alditol + 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 + 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 + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = L-glyceraldehyde + NADPH + H(+)

glycerol + 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

J Mol Biol 406:700-712 (2011)

PubMed id: 21185307

Tracing the detail: how mutations affect binding modes and thermodynamic signatures of closely related aldose reductase inhibitors.

C.Koch, A.Heine, G.Klebe.

ABSTRACT

No abstract given.