PDBsum entry: 1cnz

Oxidoreductase

PDB id: 1cnz

Contents

Protein chains

363 a.a. *

Ligands

SO4 ×8

Metals

_MN ×2

Waters ×635

* Residue conservation analysis

PDB id:

1cnz

Name:

Oxidoreductase

Title:

3-isopropylmalate dehydrogenase (ipmdh) from salmonella typhimurium

Structure:

Protein (3-isopropylmalate dehydrogenase). Chain: a, b. Synonym: ipmdh, imdh. Engineered: yes

Source:

Salmonella typhimurium. Organism_taxid: 602. Gene: leu b. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.76Å R-factor: 0.198 R-free: 0.257

Authors:

G.Wallon,G.Kryger,S.T.Lovett,T.Oshima,D.Ringe,G.A.Petsko

Key ref:

G.Wallon et al. (1997). Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus. J Mol Biol, 266, 1016-1031. PubMed id: 9086278 DOI: 10.1006/jmbi.1996.0797

Date:

24-May-99 Release date: 01-Jun-99

Protein chains

P37412  (LEU3_SALTY) -  3-isopropylmalate dehydrogenase

Seq: 363 a.a.

Struc: 363 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.85 - 3-isopropylmalate dehydrogenase.
• Pathway: Leucine Biosynthesis
• Reaction: (2R,3S)-3-isopropylmalate + NAD⁺ = 4-methyl-2-oxopentanoate + CO₂ + NADH

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: oxidation reduction (4 terms)
• Biochemical function: oxidoreductase activity (6 terms)

reference

DOI no: 10.1006/jmbi.1996.0797

J Mol Biol 266:1016-1031 (1997)

PubMed id: 9086278

Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus.

G.Wallon, G.Kryger, S.T.Lovett, T.Oshima, D.Ringe, G.A.Petsko.

ABSTRACT

The basis of protein stability has been investigated by the structural comparison of themophilic enzymes with their mesophilic counterparts. A number of characteristics have been found that can contribute to the stabilization of thermophilic proteins, but no one is uniquely capable of imparting thermostability. The crystal structure of 3-isopropylmalate dehydrogenase (IPMDH) from the mesophiles Escherichia coli and Salmonella typhimurium have been determined by the method of molecular replacement using the known structure of the homologous Thermus thermophilus enzyme. The structure of the E. coli enzyme was refined at a resolution of 2.1 A to an R-factor of 17.3%, that of the S. typhimurium enzyme at 1.7 A resolution to an R-factor of 19.8%. The three structures were compared to elucidate the basis of the higher thermostability of the T. thermophilus enzyme. A mutant that created a cavity in the hydrophobic core of the thermophilic enzyme was designed to investigate the importance of packing density for thermostability. The structure of this mutant was analyzed. The main stabilizing features in the thermophilic enzyme are an increased number of salt bridges, additional hydrogen bonds, a proportionately larger and more hydrophobic subunit interface, shortened N and C termini and a larger number of proline residues. The mutation in the hydrophobic core of T. thermophilus IPMDH resulted in a cavity of 32 A3, but no significant effect on the activity and thermostability of the mutant was observed.

Selected figure(s)

Figure 4.
Figure 4. Overlay of the C^α-backbones of the monomers of Ec (solid, black), Tt (solid, light gray) and St (broken) IPMDH. A, The “closed” form of StIPMDH overlayed on Ec/TtIPMDH. the closed form of subunit 1 of StIPMDH is similar to the active conformation of isocitrate dehydrogenase [Hurley et al 1991]. b, The “open” conformation of the three enymes. There is a 5° difference in the opening angles between the domains of Ec/TtIPMDH and subunit 2 of StIPMDH.

Figure 6.
Figure 6. Comparison of the B-factors of equivalent residues from Ec (blue), St (green, open form) and TtIPMDH (red). EcIPMDH has larger B-factor variations relative to the average, reflecting an overall flexibility in the loop regions. The open form of StIPMDH is constrained by crystal contacts and therefore is much less flexible in certain loop regions than the subunit in the closed conformation. The average B-factors are 25 Å^2 for EcIPMDH, 12 Å^2 for the open conformation of StIPMDH (20 Å^2 for the closed conformation) and 32 Å^2 for the thermophilic TtIPMDH.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 266, 1016-1031) copyright 1997.

Figures were selected by an automated process.