4GWT

Structure of racemic Pin1 WW domain cocrystallized with DL-malic acid

Summary for 4GWT

• Entry DOI: 10.2210/pdb4gwt/pdb
• Related: 2IDH 2KCF 4GWV
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, (2S)-2-hydroxybutanedioic acid (3 entities in total)
• Functional Keywords: racemic crystallization, ww domain, proline phosphoser/thr binding, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q13526
• Total number of polymer chains: 1
• Total formula weight: 4308.73

Authors

Mortenson, D.E.,Yun, H.G.,Gellman, S.H.,Forest, K.T. (deposition date: 2012-09-03, release date: 2013-10-16, Last modification date: 2023-09-13)

Primary citation

Mortenson, D.E.,Kreitler, D.F.,Yun, H.G.,Gellman, S.H.,Forest, K.T.
Evidence for small-molecule-mediated loop stabilization in the structure of the isolated Pin1 WW domain.
Acta Crystallogr.,Sect.D, 69:2506-2512, 2013

PubMed Abstract: The human Pin1 WW domain is a small autonomously folding protein that has been useful as a model system for biophysical studies of β-sheet folding. This domain has resisted previous attempts at crystallization for X-ray diffraction studies, perhaps because of intrinsic conformational flexibility that interferes with the formation of a crystal lattice. Here, the crystal structure of the human Pin1 WW domain has been obtained via racemic crystallization in the presence of small-molecule additives. Both enantiomers of a 36-residue variant of the Pin1 WW domain were synthesized chemically, and the L- and D-polypeptides were combined to afford diffracting crystals. The structural data revealed packing interactions of small carboxylic acids, either achiral citrate or a D,L mixture of malic acid, with a mobile loop region of the WW-domain fold. These interactions with solution additives may explain our success in crystallization of this protein racemate. Molecular-dynamics simulations starting from the structure of the Pin1 WW domain suggest that the crystal structure closely resembles the conformation of this domain in solution. The structural data presented here should provide a basis for further studies of this important model system.

PubMed: 24311591
DOI: 10.1107/S090744491302444X

Experimental method

X-RAY DIFFRACTION (2.25 Å)