PDBsum entry 1xf7

Transcription

PDB id: 1xf7

Contents

Protein chain

29 a.a.

Metals

_ZN

PDB id:

1xf7

Name:

Transcription

Title:

High resolution nmr structure of the wilms' tumor suppressor protein (wt1) finger 3

Structure:

Wilms' tumor protein. Chain: a. Fragment: zinc finger 3. Synonym: wt33. Wilms' tumor suppressor protein. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Other_details: synthesized by solid-phase synthesis. The sequence occurs naturally homo sapiens (human). The g28e and t29k mutations improve sample behavior without affecting the structure

NMR struc:

40 models

Authors:

M.J.Lachenmann,J.E.Ladbury,J.Dong,K.Huang,P.Carey,M.A.Weiss

Key ref:

M.J.Lachenmann et al. (2004). Why zinc fingers prefer zinc: ligand-field symmetry and the hidden thermodynamics of metal ion selectivity. Biochemistry, 43, 13910-13925. PubMed id: 15518539 DOI: 10.1021/bi0491999

Date:

14-Sep-04 Release date: 14-Dec-04

Protein chain

P19544  (WT1_HUMAN) -  Wilms tumor protein from Homo sapiens

Seq: 449 a.a.

Struc: 29 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/bi0491999

Biochemistry 43:13910-13925 (2004)

PubMed id: 15518539

Why zinc fingers prefer zinc: ligand-field symmetry and the hidden thermodynamics of metal ion selectivity.

M.J.Lachenmann, J.E.Ladbury, J.Dong, K.Huang, P.Carey, M.A.Weiss.

ABSTRACT

The zinc finger, a motif of protein-nucleic acid recognition broadly conserved among eukaryotes, is a globular minidomain containing a tetrahedral metal-binding site. Preferential coordination of Zn(2+) (relative to Co(2+)) is proposed to reflect differences in ligand-field stabilization energies (LFSEs) due to complete or incomplete occupancy of d orbitals. LFSE predicts that the preference for Zn(2+) should be purely enthalpic in accord with calorimetric studies of a high-affinity consensus peptide (CP-1; Blasie, C. A., and Berg, J. (2002) Biochemistry 41, 15068-73). Despite its elegance, the general predominance of LFSE is unclear as (i) the magnitude by which CP-1 prefers Zn(2+) is greater than that expected and (ii) the analogous metal ion selectivity of a zinc metalloenzyme (carbonic anhydrase) is driven by changes in entropy rather than enthalpy. Because CP-1 was designed to optimize zinc binding, we have investigated the NMR structure and metal ion selectivity of a natural finger of lower stability derived from human tumor-suppressor protein WT1. Raman spectroscopy suggests that the structure of the WT1 domain is unaffected by interchange of Zn(2+) and Co(2+). As in CP-1, preferential binding of Zn(2+) (relative to Co(2+)) is driven predominantly by differences in enthalpy, but in this case the enthalpic advantage is less than that predicted by LFSE. A theoretical framework is presented to define the relationship between LFSE and other thermodynamic factors, such as metal ion electroaffinities, enthalpies of hydration, and the topography of the underlying folding landscape. The contribution of environmental coupling to entropy-enthalpy compensation is delineated in a formal thermodynamic cycle. Together, these considerations indicate that LFSE provides an important but incomplete description of the stringency and thermodynamic origin of metal-ion selectivity.