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“People need to realize, or remember, that ITSM is so much more than IT service desk. Then they need to understand that ITSM is so much more than the processes covered by ITIL, the popular ITSM best practice framework. That instead ITSM is about delivering IT as a service which, in 2016 and beyond, means keeping up with the employee and customer consumer-world-driven expectations of service and support. It’s currently one of the biggest challenges for IT(SM) professionals – understanding what customer experience (CX) is, that it’s relevant inside the organization as well as outside, and what they need to do about it.”

Claire Agutter – Founder of ITSM Zone

“2016 has been the year when IT service management has changed beyond all recognition. Organisations large and small are looking at emerging practices like DevOps and agile service management and asking “can this help us do our job better?” In the next 5 years, I’m expecting to see ITSM continue to evolve to deliver good IT faster and meet business needs. ITSM experts will need tore-skilland keep learning in order to stay relevant, consultancy models will change and IT departments will converge with the businesses they serve.”

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“IT service management isn’t really about how you manage IT services, it’s about how you create value by ensuring your customers have great experiences, without having to use resources that you can’t afford”

Tony Price –Director WW IT4IT Strategic Consulting at Hewlett Packard Enterprise

“IT Service Management (ITSM) is a constant. There has been and will always be a need for it, but will the ITSM of today look the same in the next five years?Almost certainly not! The way we deploy, operate and continually improve ITSM has massively changed over the last five years and will continue to do so in the future. Who would have thought that ITSM Software would be utilising real time analytics, big data, social media and robotics, but this is the reality of today! Change will also be driven by the fact that we live in a world where almost everything is required on demand. Organisations and individuals are simply not prepared to wait as they need to see instant value to remain competitive and “in the game”. Everyone wants everything better faster cheaper and safer and ITSM is no exception. So buckle up as the ride is only just starting and thing will start to move very very fast!”

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“The notion that IT doesn’t matter anymore is particularly frustrating because everyone in the business is a technology expert, until something stops performing the way it’s supposed to. This represents a clear call to action for IT leaders, who have to shift from service providers to service brokers, who can ensure the business can connect to technology solutions safely and securely, in ways that empower, and not impair. ITSM provides the framework to accomplish those objectives and the future has never been brighter.”


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Human FMOs are FAD-containing flavoproteins comprising 532–558 amino acids (i.e., 60–65kDa proteins). Two glycine-rich motifs forming part of the Rossman folds for NADPH and FAD binding are found in the N-terminal half of the enzyme. The C-terminal portion is pronouncedly hydrophobic and may represent a membrane anchor domain. However, deletion of this hydrophobic region has generally been accompanied by loss of enzyme activity and crystallization of the protein has yet to be accomplished. Homology models based on soluble GSH reductase and/or phenylacetone monooxygenase may hold promise in the interim for visualizing some aspects of FMO structure.

Cordelia Bolle, in Plant Transcription Factors , 2016


The GRAS protein family is present not only in all higher plant species, but also in lower plants and at least one alga. Recently, it has been shown that bacterial proteins, belonging to the Rossmann-fold SAM-dependent methyltransferases, cluster with GRAS proteins. GRAS proteins are involved in many diverse signaling and developmental processes and play an important role in transcriptional control. The GRAS domain itself is highly conserved with several nearly invariant amino acids and a strict spatial distribution, suggesting the importance of these amino acids for a conserved function. In higher plants about 15 clades of GRAS proteins can be discriminated, but not all of them are present in all plant species, suggesting that adaptive processes probably played a role in the establishment and maintenance of specific clades and the numbers of members within each.

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But let us now count the occurrences of two representative classes of each superfold in different genomes: For example, yeast and archaea have almost the same numbers, but different percentages, of the Rossmann-fold S-adenosyl L-methionine (SAM)-dependent methyltransferases (respectively, 30 and 31, accounting for 0.4 and 1% of all genes in these genomes), and very different numbers and frequencies of another class of SAM-binding proteins, namely TIM barrel SAM-radical enzymes (respectively 5 and 24; Kozbial and Mushegian, 2005 ). At this level, designability must have very little to do with the observed counts of these protein families; selection for function may have played a more important role. Thus, the reasons for the existence of superfolds may be complex.

Gretchen A. Repasky 1 , ... Channing J. Der 2 4 5 , in Handbook of Cell Signaling (Second Edition) , 2010


R-Ras proteins share 46–67 percent amino acid identity with each other, and 52–55 percent amino acid identity with H-Ras ( Figure 214.2b ), primarily in the consensus guanine nucleotide binding motifs and the switch I and II regions of Ras that alter conformation based on the bound guanine nucleotide (GTP or GDP), permitting function as GDP/GTP-regulated molecular switches ( Figure 214.2a ) [9] . These strong sequence similarities account for the fact that Ras and R-Ras proteins are regulated by an overlapping set of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) ( Table 214.1 ) [10] . Like Ras, GTP-bound R-Ras is the active form, and mutations at positions analogous to those found in tumor-associated mutant Ras proteins (amino acids 12 and 61) also produce constitutively activated R-Ras GTPases. Finally, like Ras, effectors of R-Ras proteins typically contain Ras-binding (RBD) or Ras-association (RA) domains that are responsible for their preferential binding to the GTP-bound conformation.

Like Ras, R-Ras proteins contain a carboxyl-terminal CAAX tetrapeptide motif that directs posttranslational modifications, including the covalent addition of an isoprenoid lipid, which promotes the association of R-Ras proteins with the inner face of the plasma membrane [11] ( Figure 214.3 ). However, whereas Ras proteins are modified by a C15 farnesyl isoprenoid, R-Ras proteins are modified by the more hydrophobic C20 geranylgeranyl isoprenoids [12] . Isoprenoid modification of Ras and R-Ras proteins is essential for biological function. Consequently, inhibitors (FTIs) of the enzyme farnesyltransferase, which catalyzes the modification of Ras proteins, have been developed as inhibitors of oncogenic Ras function and are under clinical evaluation as anti-neoplastic drugs. Similarly, inhibitors (GGTIs) of the enzyme geranylgeranyltransferase I, which catalyzes the modification of R-Ras proteins, have also been developed, and have shown anti-tumor activity in preclinical studies [13] . TC21 can also be modified by farnesyltransferase [14] . The remaining two CAAX-signaled modifications, Rce1-catalyzed removal of the AAX peptide and Icmt-catalyzed carboxylmethylation of the prenylated cysteine residue, are also being considered for therapeutic intervention [15] .

Second, the largest families of paralogs seem to be domain specific. In almost every prokaryotic (bacterial or archaeal) proteome, the 10 largest families include Walker-type ATPases/GTPases, permeases, helix–turn–helix transcription factors, and Rossmann-fold enzymes that bind nucleotide cofactors (including NAD/NADP-dependent and FAD-dependent oxidoreductases, SAM-dependent methyltransferases, nucleosidediphosphosugar transferases, and a few other families). On the other hand, the top 10 list in eukaryotes includes the serine/threonine/tyrosine/lipid kinase superfamily, various classes of regulatory proteins with cysteine finger motifs, and, in multicellular species, Iglike domains and other modules involved in protein-protein interactions—none of which are prominent in prokaryotes. There are also species-specific expansions of individual families, such as Fe–S oxidoreductases in or proteinases of the S1 clan in Other families may experience lineage-specific reduction; for example, odorant receptor families are large in species that use olfactory communication often, such as C. or mouse, but in humans most of the paralogs are functionally inactivated ( Zozulia , 2001 ).

Lakshminarayan M. Iyer, ... L. Aravind, in Progress in Molecular Biology and Translational Science , 2011

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