How many carbonic anhydrase inhibition mechanisms exist?

Six genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) were described to date. Inhibition of CAs has pharmacologic applications in the field of antiglaucoma, anticonvulsant, anticancer, and anti-infective agents. New classes of CA inhibitors (CAIs) were described in the last decade with enzyme inhibition mechanisms differing considerably from the classical inhibitors of the sulfonamide or anion type. Five different CA inhibition mechanisms are known: (i) the zinc binders coordinate to the catalytically crucial Zn(II) ion from the enzyme active site, with the metal in tetrahedral or trigonal bipyramidal geometries. Sulfonamides and their isosters, most anions, dithiocarbamates and their isosters, carboxylates, and hydroxamates bind in this way; (ii) inhibitors that anchor to the zinc-coordinated water molecule/hydroxide ion (phenols, carboxylates, polyamines, 2-thioxocoumarins, sulfocoumarins); (iii) inhibitors which occlude the entrance to the active site cavity (coumarins and their isosters), this binding site coinciding with that where CA activators bind; (iv) compounds which bind out of the active site cavity (a carboxylic acid derivative was seen to inhibit CA in this manner), and (v) compounds for which the inhibition mechanism is not known, among which the secondary/tertiary sulfonamides as well as imatinib/nilotinib are the most investigated examples. As CAIs are used clinically in many pathologies, with a sulfonamide inhibitor (SLC-0111) in Phase I clinical trials for the management of metastatic solid tumors, this review updates the recent findings in the field which may be useful for a structure-based drug design approach of more selective/potent modulators of the activity of these enzymes.     

How many protein-protein interactions types exist in nature?

"Protein quaternary structure universe" refers to the ensemble of all protein-protein complexes across all organisms in nature. The number of quaternary folds thus corresponds to the number of ways proteins physically interact with other proteins. This study focuses on answering two basic questions: Whether the number of protein-protein interactions is limited and, if yes, how many different quaternary folds exist in nature. By all-to-all sequence and structure comparisons, we grouped the protein complexes in the protein data bank (PDB) into 3,629 families and 1,761 folds. A statistical model was introduced to obtain the quantitative relation between the numbers of quaternary families and quaternary folds in nature. The total number of possible protein-protein interactions was estimated around 4,000, which indicates that the current protein repository contains only 42% of quaternary folds in nature and a full coverage needs approximately a quarter century of experimental effort. The results have important implications to the protein complex structural modeling and the structure genomics of protein-protein interactions.     

How many lethal alleles?

Knowledge of the frequency of lethal mutant alleles in a population is important for our understanding of population genetics and evolution, and yet there have been few attempts to measure their number in wild populations. A new study has revealed unexpectedly low numbers of segregating lethal alleles in two species of fish. More experiments are needed, however, to know whether this result is general.     

How many birds are there?

Attempts to assess the magnitude of global biodiversity have focused on estimating species richness. However, this is but one component of biodiversity, and others, such as numbers of individuals or biomass, are at least as poorly known and just as important to quantify. Here, we use a variety of methods to estimate the global number of individuals for a single taxon, birds. The different methods yield surprisingly consistent estimates of a global bird population of between 200 billion and 400 billion individuals (1 billion=109). We discuss some of the implications of this figure.     

How many SNPs are enough?

Since the days of allozyme analysis, we have been enamored with the idea that if we just had enough polymorphic mendelian loci, we could gauge the inbreeding level of individuals by measuring heterozygosity and simultaneously measure the degree of genetic relatedness between pairs of individuals. Given Mendel’s Laws, we have always known that we would need numerous independently segregating loci to achieve any reasonable degree of accuracy. Santure et al. (2010, this issue) use a 771 marker SNP panel to assess heterozygosity levels and to assess pairwise relatedness, and compare both with theoretical expectations obtained from a carefully recorded pedigree of a zebra finch breeding colony, as a function of increasing numbers of SNP markers. They also compare the SNP results with those from a 20‐locus microsatellite panel, showing that adding SNPs to a fairly large microsatellite panel improves accuracy, but given an existing panel of 125 SNPs, little is to be gained by adding microsatellites. They show that the accuracy available for estimating individual levels of inbreeding is somewhat limited. They also show that the average pairwise relatedness measures bracket pedigree relationship very nicely, but the variances for individual pairs remain substantial, even with a very large panel.     

How many species of Araucarioxylon?

Fossil wood, similar to that of modern Araucariaceae, has been known for a long time, and is usually called Araucarioxylon. More than 400 morphospecies have been described, whereas this wood type displays few characteristic features. This taxonomical profusion is compounded by nomenclatural problems, Araucarioxylon being an illegitimate name. The status of the wood morphogenus, the infrageneric structure and the names that apply to the taxa designated for fossil woods of the Araucarioxylon-type are discussed. A database with 428 morphospecies designated for Araucarioxylon-type of wood is analyzed. The name Agathoxylon Hartig seems to be the most appropriate for the corresponding morphogenus. Albeit theoretically several hundred morphospecies could be recognized within this group, it is at least as probable that only one should be retained.     

How many fungi make sclerotia?

Most fungi produce some type of durable microscopic structure such as a spore that is important for dispersal and/or survival under adverse conditions, but many species also produce dense aggregations of tissue called sclerotia. These structures help fungi to survive challenging conditions such as freezing, desiccation, microbial attack, or the absence of a host. During studies of hypogeous fungi we encountered morphologically distinct sclerotia in nature that were not linked with a known fungus. These observations suggested that many unrelated fungi with diverse trophic modes may form sclerotia, but that these structures have been overlooked. To identify the phylogenetic affiliations and trophic modes of sclerotium-forming fungi, we conducted a literature review and sequenced DNA from fresh sclerotium collections. We found that sclerotium-forming fungi are ecologically diverse and phylogenetically dispersed among 85 genera in 20 orders of Dikarya, suggesting that the ability to form sclerotia probably evolved ≥14 different times in fungi.     

How many species are there?

How many species are there is a question receiving more attention from biologists and reasons for this are suggested. Different methods of answering this question are examined and include: counting all species; extrapolations from known faunas and regions; extrapolations from samples; methods using ecological models; censusing taxonomists' views. Most of these methods indicate that global totals of 5 to 15 million species are reasonable. The implications of much higher estimates of 30 million species or more are examined, particularly the question of where these millions of species might be found.     

How many genes in a genome?

Despite the current good level of annotation, the Drosophila genome still holds surprises. A recent study has added perhaps 2,000 genes to the predicted total, and raises a number of questions about how genome annotation data should be stored and presented.     

How many membrane proteins are there?

One of the basic issues that arises in functional genomics is the ability to predict the subcellular location of proteins that are deduced from gene and genome sequencing. In particular, one would like to be able to readily specify those proteins that are soluble and those that are inserted in a membrane. Traditional methods of distinguishing between these two locations have relied on extensive, time-consuming biochemical studies. The alternative approach has been to make inferences based on a visual search of the amino acid sequences of presumed gene products for stretches of hydrophobic amino acids. This numerical, sequence-based approach is usually seen as a first approximation pending more reliable biochemical data. The recent availability of large and complete sequence data sets for several organisms allows us to determine just how accurate such a numerical approach could be, and to attempt to minimize and quantify the error involved. We have optimized a statistical approach to protein location determination. Using our approach, we have determined that surprisingly few proteins are misallocated using the numerical method. We also examine the biological implications of the success of this technique.     

How many possums make a cow?

The importance of possums as competitors with livestock for pasture is sometimes used as justification for possum control. Unfortunately a confusion of wet and dry weight values of pasture and daily consumption by possums appears to have resulted in a significant overestimate of the economic costs of possums as pasture pests. A correctly estimated daily dry matter intake of pasture by possums is 0.0144 kg pasture dry matter per possum per day. For a possum density of 1 ha^-1, this amounts to a reduction of about 1% of a stock unit ha^-1 year^-1. At higher possum densities, which often occur on farms adjacent to forest or scrub, losses would be correspondingly higher. A more direct way to measure possum impact on pasture production would be to use exclosures.     

How many species of Cladocera are there?

An estimation of the number of taxa within families, genera and local faunas of Cladocera reveals that only c. 129 species (17% of all known species) may be considered as sufficiently well described (valid species), and c. 146 as rather well described (fair species) but needing further study using modern methods of investigation. The status of all other species is vague. The families Chydoridae, Daphniidae and Sididae and genera Diaphanosoma, Daphnia, (including Daphniopsis), Megafenestra, Scapholeberis, Eurycercus, Chydorus, Ephemeroporus and Pleuroxus have been comparatively studied best. The largest number of valid species is known from Europe, North America, Australia and South America, and the smallest number from Africa. Presence of large number of vague species of Cladocera negatively affects faunistic, zoogeographic, and ecological studies of continental waters.Dedicated to the memory of Professor D. J. Frey     

How many hydrogen-bonded α-turns are possible?

The formation of α-turns is a possibility to reverse the direction of peptide sequences via five amino acids. In this paper, a systematic conformational analysis was performed to find the possible isolated α-turns with a hydrogen bond between the first and fifth amino acid employing the methods of ab initio MO theory in vacuum (HF/6-31G*, B3LYP/6-311?+?G*) and in solution (CPCM/HF/6-31G*). Only few α-turn structures with glycine and alanine backbones fulfill the geometry criteria for the i←(i?+?4) hydrogen bond satisfactorily. The most stable representatives agree with structures found in the Protein Data Bank. There is a general tendency to form additional hydrogen bonds for smaller pseudocycles corresponding to β- and γ-turns with better hydrogen bond geometries. Sometimes, this competition weakens or even destroys the i←(i?+?4) hydrogen bond leading to very stable double β-turn structures. This is also the reason why an “ideal” α-turn with three central amino acids having the perfect backbone angle values of an α-helix could not be localized. There are numerous hints for stable α-turns with a distance between the \( {{\hbox{C}}_\alpha } \)-atoms of the first and fifth amino acid smaller than 6-7 Å, but without an i←(i?+?4) hydrogen bond.