PDBsum entry 5hvq

Ligase

PDB id: 5hvq

Contents

Protein chains

197 a.a.

236 a.a.

Metals

_ZN ×2

PDB id:

5hvq

Name:

Ligase

Title:

Alternative model of the mage-g1 nse-1 complex

Structure:

Melanoma-associated antigen g1. Chain: d. Synonym: hepatocellular carcinoma-associated protein 4,mage-g1 antigen,necdin-like protein 2. Engineered: yes. Non-structural maintenance of chromosomes element 1 homolog. Chain: c. Synonym: non-smc element 1 homolog.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ndnl2, hca4, mageg1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: nsmce1, hspc333, hspc337. Expression_system_taxid: 562

Resolution:

2.92Å R-factor: 0.238 R-free: 0.268

Authors:

J.A.Newman,C.D.O.Cooper,A.K.Roos,H.Aitkenhead,U.C.T.Oppermann, H.J.Cho,R.Osman,O.Gileadi

Key ref:

J.A.Newman et al. (2016). Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding. Plos One, 11, e0148762. PubMed id: 26910052 DOI: 10.1371/journal.pone.0148762

Date:

28-Jan-16 Release date: 26-Oct-16

Protein chain

Q96MG7  (NSE3_HUMAN) -  Non-structural maintenance of chromosomes element 3 homolog from Homo sapiens

Seq: 304 a.a.

Struc: 197 a.a.*

Protein chain

Q8WV22  (NSE1_HUMAN) -  Non-structural maintenance of chromosomes element 1 homolog from Homo sapiens

Seq: 266 a.a.

Struc: 236 a.a.

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

Enzyme reactions

• Enzyme class 2: Chain C: 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
• Enzyme class 3: Chain D: E.C.?

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.

DOI no: 10.1371/journal.pone.0148762

Plos One 11:e0148762 (2016)

PubMed id: 26910052

Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding.

J.A.Newman, C.D.Cooper, A.K.Roos, H.Aitkenhead, U.C.Oppermann, H.J.Cho, R.Osman, O.Gileadi.

ABSTRACT

The MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis. Here we determined the crystal structures of MAGE-A3 and MAGE-A4. Both proteins crystallized with a terminal peptide bound in a deep cleft between two tandem-arranged winged helix domains. MAGE-A3 (but not MAGE-A4), is predominantly dimeric in solution. Comparison of MAGE-A3 and MAGE-A3 with a structure of an effector-bound MAGE-G1 suggests that a major conformational rearrangement is required for binding, and that this conformational plasticity may be targeted by allosteric binders.