MolProbity: all-atom contacts and structure validation for proteins and nucleic acids

Davis, Ian; Leaver‐Fay, Andrew; Chen, Vincent B.; Block, Jeremy N.; Kapral, Gary J.; Wang, Xueyi; Murray, Laura W.; Arendall, W.B.; Snoeyink, Jack; Richardson, Jane S.; Richardson, David C.

doi:10.1093/nar/gkm216

Cited by 3,608 publications

(3,217 citation statements)

References 35 publications

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“…36 Later refinement included TLS refinement (using TLSMD 37 parameters), followed by a final refinement using hydrogens added with Molprobity. 38 …”

Section: Resultsmentioning

confidence: 99%

Cysteine‐free rop: A four‐helix bundle core mutant has wild‐type stability and structure but dramatically different unfolding kinetics

et al. 2010

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Cysteine residues can complicate the folding and storage of proteins due to improper formation of disulfide bonds or oxidation of residues that are natively reduced. Wild-type Rop is a homodimeric four-helix bundle protein and an important model for protein design in the understanding of protein stability, structure and folding kinetics. In the native state, Rop has two buried, reduced cysteine residues in its core, but these are prone to oxidation in destabilized variants, particularly upon extended storage. To circumvent this problem, we designed and characterized a Cys-free variant of Rop, including solving the 2.3 Å X-ray crystal structure. We show that the C38A C52V variant has similar structure, stability and in vivo activity to wild-type Rop, but that it has dramatically faster unfolding kinetics like virtually every other mutant of Rop that has been characterized. This cysteine-free Rop has already proven useful for studies on solution topology and on the relationship of core mutations to stability. It also suggests a general strategy for removal of pairs of Cys residues in proteins, both to make them more experimentally tractable and to improve their storage properties for therapeutic or industrial purposes.

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“…36 Later refinement included TLS refinement (using TLSMD 37 parameters), followed by a final refinement using hydrogens added with Molprobity. 38 …”

Section: Resultsmentioning

confidence: 99%

Cysteine‐free rop: A four‐helix bundle core mutant has wild‐type stability and structure but dramatically different unfolding kinetics

et al. 2010

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“…Data processing and model refinement statistics are summarized in Table I. Structure quality was assessed with MolProbity 30 and the final analysis results were included in the file deposited to the Protein Data Bank.…”

Section: Methodsmentioning

confidence: 99%

Crystal structure of the C‐terminal domain of the Salmonella type III secretion system export apparatus protein InvA

2010

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InvA is a prominent inner-membrane component of the Salmonella type III secretion system (T3SS) apparatus, which is responsible for regulating virulence protein export in pathogenic bacteria. InvA is made up of an N-terminal integral membrane domain and a C-terminal cytoplasmic domain that is proposed to form part of a docking platform for the soluble export apparatus proteins notably the T3SS ATPase InvC. Here, we report the novel crystal structure of the C-terminal domain of Salmonella InvA which shows a compact structure composed of four subdomains. The overall structure is unique although the first and second subdomains exhibit structural similarity to the peripheral stalk of the A/V-type ATPase and a ring building motif found in other T3SS proteins respectively.

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“…To evaluate the impact of NR5A1 nonsynonymous mutations at the tertiary protein structure, several structural models were built for wild‐type and mutated molecules in the YASARA suite (Krieger et al, 2004), using as templates the crystal structures of the human liver receptor homologue 1 (LRH‐1, NR5A2) DNA‐binding domain (DBD) in complex with the hCYP7A1 promoter (PDB accession code 2A66), and the human NR5A1 ligand‐binding domain (LBD) in complex with di‐pamitoyl‐3‐SN‐phosphatidylethanolamine (PDB accession code 1ZDT). Stereo chemical quality of generated structural models was accessed with MOLPROBITY (Davis et al, 2007). Two molecular mechanics simulations were carried in explicit solvent for each model.…”

Section: Molecular Analysismentioning

confidence: 99%

Wide spectrum of NR5A1‐related phenotypes in 46,XY and 46,XX individuals

Domenice¹,

Machado²,

Ferreira

et al. 2016

Birth Defects Research Pt C

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Steroidogenic factor 1 (NR5A1, SF‐1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1‐related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype‐phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian‐determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1‐related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever‐expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309–320, 2016. © 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.

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MolProbity: all-atom contacts and structure validation for proteins and nucleic acids

Cited by 3,608 publications

References 35 publications

Cysteine‐free rop: A four‐helix bundle core mutant has wild‐type stability and structure but dramatically different unfolding kinetics

Cysteine‐free rop: A four‐helix bundle core mutant has wild‐type stability and structure but dramatically different unfolding kinetics

Crystal structure of the C‐terminal domain of the Salmonella type III secretion system export apparatus protein InvA

Wide spectrum of NR5A1‐related phenotypes in 46,XY and 46,XX individuals

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