PDBsum entry 2k2d

Metal binding protein

PDB id: 2k2d

Contents

Protein chain

47 a.a. *

Metals

_ZN

* Residue conservation analysis

PDB id:

2k2d

Name:

Metal binding protein

Title:

Solution nmr structure of c-terminal domain of human pirh2. Northeast structural genomics consortium (nesg) target ht2c

Structure:

Ring finger and chy zinc finger domain-containing protein 1. Chain: a. Fragment: c-terminal domain: residues 187-261. Synonym: zinc finger protein 363, ch-rich-interacting match with plag1, androgen receptor n-terminal-interacting protein, p53-induced ring-h2 protein, hpirh2, ring finger protein 199. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rchy1, arnip, chimp, pirh2, rnf199, znf363. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

15 models

Authors:

A.Lemak,Y.Sheng,M.Karra,S.Srisailam,R.C.Laister,S.Duan, C.H.Arrowsmith,Northeast Structural Genomics Consortium (Nesg)

Key ref:

Y.Sheng et al. (2008). Molecular basis of Pirh2-mediated p53 ubiquitylation. Nat Struct Biol, 15, 1334-1342. PubMed id: 19043414 DOI: 10.1038/nsmb.1521

Date:

31-Mar-08 Release date: 15-Apr-08

Protein chain

Q96PM5  (ZN363_HUMAN) -  RING finger and CHY zinc finger domain-containing protein 1 from Homo sapiens

Seq: 261 a.a.

Struc: 47 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1038/nsmb.1521

Nat Struct Biol 15:1334-1342 (2008)

PubMed id: 19043414

Molecular basis of Pirh2-mediated p53 ubiquitylation.

Y.Sheng, R.C.Laister, A.Lemak, B.Wu, E.Tai, S.Duan, J.Lukin, M.Sunnerhagen, S.Srisailam, M.Karra, S.Benchimol, C.H.Arrowsmith.

ABSTRACT

Pirh2 (p53-induced RING-H2 domain protein; also known as Rchy1) is an E3 ubiquitin ligase involved in a negative-feedback loop with p53. Using NMR spectroscopy, we show that Pirh2 is a unique cysteine-rich protein comprising three modular domains. The protein binds nine zinc ions using a variety of zinc coordination schemes, including a RING domain and a left-handed beta-spiral in which three zinc ions align three consecutive small beta-sheets in an interleaved fashion. We show that Pirh2-p53 interaction is dependent on the C-terminal zinc binding module of Pirh2, which binds to the tetramerization domain of p53. As a result, Pirh2 preferentially ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein turnover of the transcriptionally active form of p53.

Selected figure(s)

Figure 2.
(a) Pirh2 NTD. N lobe shows the interleaved Zn1 and Zn2 sites and a four-cysteine-coordinated Zn3 site. C lobe shows left-handed -spiral structure with three CCHC motifs coordinating Zn4, Zn5 and Zn6. (b) Pirh2 RING domain, showing the interleaved Zn7 and Zn8 sites. (c) Pirh2 CTD, showing Zn9 site coordinated by four cysteines. The nine zinc atoms are shown as spheres.

Figure 7.
Top, domains of tetrameric p53 interacting with those of Pirh2. UBE2D2-Pirh2 RING domain orientations are based on the crystal structure of the homologous complex formed between UBCH7 and the c-Cbl RING domain^20. Bottom, active site cysteine of UBE2D2, charged with ubiquitin, is shown in red.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2008, 15, 1334-1342) copyright 2008.

Figures were selected by an automated process.