PDBsum entry 7b51

Nuclear protein

PDB id: 7b51

Contents

Protein chains

174 a.a.

1013 a.a.

Ligands

GTP

BME

Metals

_MG

Waters ×136

PDB id:

7b51

Name:

Nuclear protein

Title:

Crystal structure of human crm1 covalently modified by 2- mercaptoethanol at cys528

Structure:

Gtp-binding nuclear protein ran. Chain: b. Synonym: androgen receptor-associated protein 24,gtpase ran,ras-like protein tc4,ras-related nuclear protein. Engineered: yes. Exportin-1. Chain: a. Synonym: exp1,chromosome region maintenance 1 protein homolog. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ran, ara24, ok/sw-cl.81. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: xpo1, crm1. Expression_system_taxid: 562

Resolution:

2.58Å R-factor: 0.216 R-free: 0.250

Authors:

A.Shaikhqasem,R.Ficner

Key ref:

A.Shaikhqasem et al. (2021). Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP. Acta Crystallogr F Struct Biol Commun, 77, 70-78. PubMed id: 33682791 DOI: 10.1107/S2053230X2100203X

Date:

03-Dec-20 Release date: 10-Mar-21

Protein chain

P62826  (RAN_HUMAN) -  GTP-binding nuclear protein Ran from Homo sapiens

Seq: 216 a.a.

Struc: 174 a.a.*

Protein chain

O14980  (XPO1_HUMAN) -  Exportin-1 from Homo sapiens

Seq: 1071 a.a.

Struc: 1013 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain A: E.C.?
• Enzyme class 3: Chain B: E.C.3.6.5.- - ?????

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: 10.1107/S2053230X2100203X

Acta Crystallogr F Struct Biol Commun 77:70-78 (2021)

PubMed id: 33682791

Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP.

A.Shaikhqasem, K.Schmitt, O.Valerius, R.Ficner.

ABSTRACT

CRM1 is a nuclear export receptor that has been intensively targeted over the last decade for the development of antitumor and antiviral drugs. Structural analysis of several inhibitor compounds bound to CRM1 revealed that their mechanism of action relies on the covalent modification of a critical cysteine residue (Cys528 in the human receptor) located in the nuclear export signal-binding cleft. This study presents the crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP at 2.58 Å resolution. The results demonstrate that buffer components can interfere with the characterization of cysteine-dependent inhibitor compounds.