PMID- 26754054
OWN - NLM
STAT- MEDLINE
DCOM- 20161230
LR  - 20190109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jan 12
TI  - Computational analysis of prolyl hydroxylase domain-containing protein 2 (PHD2) 
      mutations promoting polycythemia insurgence in humans.
PG  - 18716
LID - 10.1038/srep18716 [doi]
LID - 18716
AB  - Idiopathic erythrocytosis is a rare disease characterized by an increase in red 
      blood cell mass due to mutations in proteins of the oxygen-sensing pathway, such 
      as prolyl hydroxylase 2 (PHD2). Here, we present a bioinformatics investigation 
      of the pathological effect of twelve PHD2 mutations related to polycythemia 
      insurgence. We show that few mutations impair the PHD2 catalytic site, while most 
      localize to non-enzymatic regions. We also found that most mutations do not 
      overlap the substrate recognition site, suggesting a novel PHD2 binding 
      interface. After a structural analysis of both binding partners, we suggest that 
      this novel interface is responsible for PHD2 interaction with the LIMD1 tumor 
      suppressor.
FAU - Minervini, Giovanni
AU  - Minervini G
AD  - Department of Biomedical Sciences and CRIBI Biotechnology Center, University of 
      Padova, Viale G. Colombo 3, 35121, Padova, Italy.
FAU - Quaglia, Federica
AU  - Quaglia F
AD  - Department of Biomedical Sciences and CRIBI Biotechnology Center, University of 
      Padova, Viale G. Colombo 3, 35121, Padova, Italy.
FAU - Tosatto, Silvio C E
AU  - Tosatto SC
AD  - Department of Biomedical Sciences and CRIBI Biotechnology Center, University of 
      Padova, Viale G. Colombo 3, 35121, Padova, Italy.
AD  - CNR Institute of Neuroscience, Viale G. Colombo 3, 35121, Padova, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160112
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - EC 1.14.11.2 (EGLN1 protein, human)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Conserved Sequence
MH  - Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases/chemistry/*genetics/metabolism
MH  - Models, Molecular
MH  - *Mutation
MH  - Mutation, Missense
MH  - Polycythemia/*genetics/metabolism
MH  - Position-Specific Scoring Matrices
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Interaction Mapping
MH  - Protein Interaction Maps
MH  - Protein Stability
MH  - Sequence Analysis, DNA
PMC - PMC4709589
EDAT- 2016/01/13 06:00
MHDA- 2016/12/31 06:00
PMCR- 2016/01/12
CRDT- 2016/01/13 06:00
PHST- 2015/08/13 00:00 [received]
PHST- 2015/11/06 00:00 [accepted]
PHST- 2016/01/13 06:00 [entrez]
PHST- 2016/01/13 06:00 [pubmed]
PHST- 2016/12/31 06:00 [medline]
PHST- 2016/01/12 00:00 [pmc-release]
AID - srep18716 [pii]
AID - 10.1038/srep18716 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jan 12;6:18716. doi: 10.1038/srep18716.