PDBsum entry 1xcb

DNA binding protein

PDB id: 1xcb

Contents

Protein chains

(+ 0 more) 205 a.a. *

192 a.a. *

Ligands

NAD ×7

Metals

_CA ×5

* Residue conservation analysis

PDB id:

1xcb

Name:

DNA binding protein

Title:

X-ray structure of a rex-family repressor/nadh complex from thermus aquaticus

Structure:

Redox-sensing transcriptional repressor rex. Chain: a, b, c, d, e, f, g. Synonym: t-rex. Engineered: yes

Source:

Thermus aquaticus. Organism_taxid: 271. Gene: rex. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.90Å R-factor: 0.228 R-free: 0.276

Authors:

E.A.Sickmier,D.Brekasis,S.Paranawithana,J.B.Bonanno,S.K.Burley, M.S.Paget,C.L.Kielkopf,New York Sgx Research Center For Structural Genomics (Nysgxrc)

Key ref:

E.A.Sickmier et al. (2005). X-ray structure of a Rex-family repressor/NADH complex insights into the mechanism of redox sensing. Structure, 13, 43-54. PubMed id: 15642260 DOI: 10.1016/j.str.2004.10.012

Date:

01-Sep-04 Release date: 28-Sep-04

Supersedes:

1r72

Protein chains

Q9X2V5  (REX_THEAQ) -  Redox-sensing transcriptional repressor Rex from Thermus aquaticus

Seq: 211 a.a.

Struc: 205 a.a.

Protein chain

Q9X2V5  (REX_THEAQ) -  Redox-sensing transcriptional repressor Rex from Thermus aquaticus

Seq: 211 a.a.

Struc: 192 a.a.

DOI no: 10.1016/j.str.2004.10.012

Structure 13:43-54 (2005)

PubMed id: 15642260

X-ray structure of a Rex-family repressor/NADH complex insights into the mechanism of redox sensing.

E.A.Sickmier, D.Brekasis, S.Paranawithana, J.B.Bonanno, M.S.Paget, S.K.Burley, C.L.Kielkopf.

ABSTRACT

The redox-sensing repressor Rex regulates transcription of respiratory genes in response to the intra cellular NADH/NAD(+) redox poise. As a step toward elucidating the molecular mechanism of NADH/NAD(+) sensing, the X-ray structure of Thermus aquaticus Rex (T-Rex) bound to effector NADH has been determined at 2.9 A resolution. The fold of the C-terminal domain of T-Rex is characteristic of NAD(H)-dependent enzymes, whereas the N-terminal domain is similar to a winged helix DNA binding motif. T-Rex dimerization is primarily mediated by "domain-swapped" alpha helices. Each NADH molecule binds to the C-terminal domain near the dimer interface. In contrast to NAD(H)-dependent enzymes, the nicotinamide is deeply buried within a hydrophobic pocket that appears to preclude substrate entry. We show that T-Rex binds to the Rex operator, and NADH but not NAD(+) inhibits T-Rex/DNA binding activity. A mechanism for redox sensing by Rex family members is proposed by analogy with domain closure of NAD(H)-dependent enzymes.

Selected figure(s)

Figure 6.
Figure 6. The T-Rex NAD(H) Binding Sites and Comparison with NAD(H)-Dependent Dehydrogenase
(A) T-Rex interactions with the NADH effector molecule, in the conformation with Phe189 inserted between the nicotinamide rings. Average distances between interacting atoms of the three subunits exhibiting this conformation are indicated.
(B) T-Rex interactions with the NADH' molecule bound to the opposite subunit, in the conformation with Phe189 folded back and buried within the hydrophobic core.
(C) LADH interactions with bound NADH, zinc ion (ZN), and DMSO substrate.

The above figure is reprinted by permission from Cell Press: Structure (2005, 13, 43-54) copyright 2005.

Figure was selected by an automated process.