PDBsum entry 6yw3

Oxidoreductase

PDB id: 6yw3

Contents

Protein chains

223 a.a.

14 a.a.

17 a.a.

Ligands

OGA

GOL

SO4

Metals

_MN

Waters ×116

PDB id:

6yw3

Name:

Oxidoreductase

Title:

Hif prolyl hydroxylase 2 (phd2/ egln1) in complex with n-oxalyl glycine (nog), hif-1alpha codd (556-574) and a rapid-derived cyclic peptide 3c (14-mer)

Structure:

Egl nine homolog 1. Chain: a. Synonym: hypoxia-inducible factor prolyl hydroxylase 2,hph-2,prolyl hydroxylase domain-containing protein 2,phd2,sm-20. Engineered: yes. Other_details: catalytic domain (residues 181-407). Phd2-specific rapid cyclic peptide 3c (14-mer). Chain: b. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: egln1, c1orf12, pnas-118, pnas-137. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Resolution:

2.28Å R-factor: 0.190 R-free: 0.208

Authors:

R.Chowdhury,C.J.Schofield

Key ref:

R.Chowdhury et al. (2020). Use of cyclic peptides to induce crystallization: case study with prolyl hydroxylase domain 2. Sci Rep, 10, 21964. PubMed id: 33319810 DOI: 10.1038/s41598-020-76307-8

Date:

29-Apr-20 Release date: 30-Dec-20

Protein chain

Q9GZT9  (EGLN1_HUMAN) -  Egl nine homolog 1 from Homo sapiens

Seq: 426 a.a.

Struc: 223 a.a.

Protein chain

No UniProt id for this chain

Struc: 14 a.a.

Protein chain

Q16665  (HIF1A_HUMAN) -  Hypoxia-inducible factor 1-alpha from Homo sapiens

Seq: 826 a.a.

Struc: 17 a.a.

Enzyme reactions

• Enzyme class 1: Chain A: E.C.1.14.11.29 - hypoxia-inducible factor-proline dioxygenase.
• Reaction: L-prolyl-[hypoxia-inducible factor alpha subunit] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-prolyl-[hypoxia-inducible factor alpha subunit] + succinate + CO2
• Cofactor: Fe(2+); L-ascorbate

Fe(2+) L-ascorbate (Bound ligand (Het Group name = GOL) matches with 50.00% similarity)

• Enzyme class 2: Chain S: 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.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/s41598-020-76307-8

Sci Rep 10:21964 (2020)

PubMed id: 33319810

Use of cyclic peptides to induce crystallization: case study with prolyl hydroxylase domain 2.

R.Chowdhury, M.I.Abboud, T.E.McAllister, B.Banerji, B.Bhushan, J.L.Sorensen, A.Kawamura, C.J.Schofield.

ABSTRACT

Crystallization is the bottleneck in macromolecular crystallography; even when a protein crystallises, crystal packing often influences ligand-binding and protein-protein interaction interfaces, which are the key points of interest for functional and drug discovery studies. The human hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) readily crystallises as a homotrimer, but with a sterically blocked active site. We explored strategies aimed at altering PHD2 crystal packing by protein modification and molecules that bind at its active site and elsewhere. Following the observation that, despite weak inhibition/binding in solution, succinamic acid derivatives readily enable PHD2 crystallization, we explored methods to induce crystallization without active site binding. Cyclic peptides obtained via mRNA display bind PHD2 tightly away from the active site. They efficiently enable PHD2 crystallization in different forms, both with/without substrates, apparently by promoting oligomerization involving binding to the C-terminal region. Although our work involves a specific case study, together with those of others, the results suggest that mRNA display-derived cyclic peptides may be useful in challenging protein crystallization cases.