THE JOURNAL OF BIOLOGICAL CHEMISTRY: The Biochemical Behavior of LeadL I. Influence of Calcium, Phosphorus, and Vitamin D on Lead in Blood and Bone

Granules of the Human Neutrophilic Polymorphonuclear Leukocyte

Iterative model-building, structure refinement, and density modification with the PHENIX AutoBuild Wizard Thomas C. Terwilliger a* , Ralf W. Grosse-Kunstleve b , Pavel V. Afonine b , Nigel W. Moriarty b , Peter Zwart b , Li-Wei Hung a , Randy J. Read c , Paul D. Adams b* a b Los Alamos National Laboratory, Mailstop M888, Los Alamos, NM 87545, USA Lawrence Berkeley National Laboratory, One Cyclotron Road, Bldg 64R0121, Berkeley, CA 94720, USA. c Department of Haematology, University of Cambridge, Cambridge CB2 0XY, UK. * Email: terwill@lanl.gov or PDAdams@lbl.gov Running title: The PHENIX AutoBuild Wizard Abstract The PHENIX AutoBuild Wizard is a highly automated tool for iterative model- building, structure refinement and density modification using RESOLVE or TEXTAL model- building, RESOLVE statistical density modification, and phenix.refine structure refinement. Recent advances in the AutoBuild Wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model completion algorithms, and automated solvent molecule picking. Model completion algorithms in the AutoBuild Wizard include loop-building, crossovers between chains in different models of a structure, and side-chain optimization. The AutoBuild Wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 A to 3.2 A, resulting in a mean R-factor of 0.24 and a mean free R factor of 0.29. The R-factor of the final model is dependent on the quality of the starting electron density, and relatively independent of resolution. Keywords: Model building; model completion; macromolecular models; Protein Data Bank; structure refinement; PHENIX Introduction Iterative model-building and refinement is a powerful approach to obtaining a complete and accurate macromolecular model. The approach consists of cycles of building an atomic model based on an electron density map for a macromolecular structure, refining the structure, using the refined structure as a basis for improving the map, and building a new model. This type of approach has been carried out in a semi-automated fashion for many years, with manual model-building iterating with automated refinement (Jensen, 1997). More recently, with the development first of ARP/wARP (Perrakis et al., 1999), and later other procedures including RESOLVE iterative model-building and refinement (Terwilliger,

Iterative model-building, structure refinement, and density modification with the PHENIX AutoBuild Wizard

https://www.cell.com/trends/immunology/pdf/S1471-4906(09)00005-2.pdf

AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense

Over the last decade, the concept of an IGFBP family has been well accepted, based on structural similarities and on functional abilities to bind IGFs with high affinities. The existence of other potential IGFBPs was left open. The discovery of proteins with N-terminal domains bearing striking structural similarities to the N terminus of the IGFBPs, and with reduced, but demonstrable, affinity for IGFs, raised the question of whether these proteins were "new" IGFBPs (22, 23, 217). The N-terminal domain had been uniquely associated with the IGFBPs and has long been considered to be critical for IGF binding. No other function has been confirmed for this domain to date. Thus, the presence of this important IGFBP domain in the N terminus of other proteins must be considered significant. Although these other proteins appear capable of binding IGF, their relatively low affinity and the fact that their major biological actions are likely to not directly involve the IGF peptides suggest that they probably should not be classified within the IGFBP family as provisionally proposed (22, 23). The conservation of this single domain, so critical to high-affinity binding of IGF by the six IGFBPs, in all of the IGFBP-rPs, as well, speaks to its biological importance. Historically, and perhaps, functionally, this has led to the designation of an "IGFBP superfamily". The classification and nomenclature for the IGFBP superfamily, are, of course, arbitrary; what is ultimately relevant is the underlying biology, much of which still remains to be deciphered. The nomenclature for the IGFBP related proteins was derived from a consensus of researchers working in the IGFBP field (52). Obviously, a more general consensus on nomenclature, involving all groups working on each IGFBP-rP, has yet to be reached. Further understanding of the biological functions of each protein should help resolve the nomenclature dilemma. For the present, redesignating these proteins IGFBP-rPs simplifies the multiple names already associated with each IGFBP related protein, and reinforces the concept of a relationship with the IGFBPs. Beyond the N-terminal domain, there is a lack of structural similarity between the IGFBP-rPs and IGFBPs. The C-terminal domains do share similarities to other internal domains found in numerous other proteins. For example, the similarity of the IGFBP C terminus to the thyroglobulin type-I domain shows that the IGFBPs are also structurally related to numerous other proteins carrying the same domain (87). Interestingly, the functions of the different C-terminal domains in members of the IGFBP superfamily include interactions with the cell surface or ECM, suggesting that, even if they share little sequence similarities, the C-terminal domains may be functionally related. The evolutionary conservation of the N-terminal domain and functional studies support the notion that IGFBPs and IGFBP-rPs together form an IGFBP superfamily. A superfamily delineates between closely related (classified as a family) and distantly related proteins. The IGFBP superfamily is therefore composed of distantly related families. The modular nature of the constituents of the IGFBP superfamily, particularly their preservation of an highly conserved N-terminal domain, seems best explained by the process of exon shuffling of an ancestral gene encoding this domain. Over the course of evolution, some members evolved into high-affinity IGF binders and others into low-affinity IGF binders, thereby conferring on the IGFBP superfamily the ability to influence cell growth by both IGF-dependent and IGF-independent means (Fig. 10). A final word, from Stephen Jay Gould (218): "But classifications are not passive ordering devices in a world objectively divided into obvious categories. Taxonomies are human decisions imposed upon nature--theories about the causes of nature's order. The chronicle of historical changes in classification provides our finest insight into conceptual revolutions

/pdf/the-insulin-like-growth-factor-binding-protein-igfbp-41vwms7yip.pdf

The insulin-like growth factor-binding protein (IGFBP) superfamily.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2893%2980118-E

Participation of cathepsin L on bone resorption

Thyroglobulin type-1 domain is a structural element found in a variety of functionally unrelated proteins. It may occur singly, as in insulin-like growth factor binding proteins, or multiply up to eleven, as in thyroglobulin. Some of these type-1 domain containing proteins have been shown to have the ability to inhibit either cysteine or cation-dependent proteinases. For these inhibitory proteins we proposed the term thyropins. These inhibitors originate from a variety of organisms and presumably have different biological functions. One of those whose function has been studied is the p41 invariant chain fragment. In vivo it associates with the major histocompatibility complex (MHC) class II molecule. The evidence supporting its involvement as a controlling factor in the process of antigen presentation is described.

Thyropins--new structurally related proteinase inhibitors.

Equistatin, a new inhibitor of cysteine proteinases from Actinia equina, is structurally related to thyroglobulin type-1 domain.

Thyroglobulin Type-1 Domains in Equistatin Inhibit Both Papain-like Cysteine Proteinases and Cathepsin D

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2891%2980295-E

Brigita Lenarčič

Papers

Participation of cathepsin L on bone resorption

Thyropins--new structurally related proteinase inhibitors.

Equistatin, a new inhibitor of cysteine proteinases from Actinia equina, is structurally related to thyroglobulin type-1 domain.

Thyroglobulin Type-1 Domains in Equistatin Inhibit Both Papain-like Cysteine Proteinases and Cathepsin D

Inactivation of human cystatin C and kininogen by human cathepsin D