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Streptococcus pyogenes Quinolinate-Salvage Pathway – Structural and Functional Studies of Quinolinate Phosphoribosyl Transferase and NH3- dependent NAD+ Synthetase

Clustering Analysis of the NadC Homologs – Clustering classification of the sequences was carried out to visualize groups of more similar sequences and similarities between them. SpNadC is composed of two domains: a quinolinate phosphoribosyl transferase, N-terminal domain (QRPTase_N (PF02749)), and a quinolinate phosphoribosyl transferase, C-terminal domain (QRPTase_C (PF01729)). Therefore, in order to perform sequence similarity based clustering of its homologs, full length sequences of proteins from both Pfam families were downloaded and merged, followed by the removal of redundant sequences.

Nicotinate-nucleotide pyrophosphorylases show high internal similarity, with dispersed bacterial and archaeal sequences, where the subgroup of molybdenum utilization proteins (ModD) can be distinguished. Eukaryotic nicotinate-nucleotide pyrophosphorylases form a more clearly separated group (Fig. 5). The group of nicotinate phosphoribosyltransferases, represented by structurally characterized proteins from Thermoplasma acidophilum (PDB code: 1YTD) and Pyrococcus furiosus (PDB code: 2I14) is clearly isolated and detaches from all the other sequences when more stringent P- values are applied.

SpNadE Structure – The NadE structure bound to Mg2+ and SO42- ions (spNadEsulf) was the first of the NadE structures to be determined (Fig. 6). The protein crystallized in primitive orthorhombic system and P212121 space group with two protein chains in the asymmetric unit. The structure was determined at 2.5 Å resolution. The model of the structure includes a dimer and the protein chains include residues 9-214 and 229- 282. Residues 215-228 from the highly conserved active site loop, are missing in both structures, which indicates that they are disordered in the absence of substrates. Similarly, the polyhistidine tags were also not modeled, as there is no visible electron density that corresponds to this fragment of the molecule.

The spNadEsulf structure was used as a starting model during the determination of the spNadE- apo structure. The spNadE-apo structure was determined at 2.1 Å resolution, and the final model was refined to Rcryst value of 0.168 and an Rfree of 0.212. The model included residues 9-96, 98-215, 228- 282 for each of the protein chains that form the dimer, present in the asymmetric unit. According to PDBePISA calculations, the dimer interface for spNadE-apo and the same interface for spNadEsulf covers 2407 Å2.

The single chain of spNadE has primarily alpha helical character with eleven alpha helices, three parallel beta strands and two 310 helices. The sequence and structure based searches revealed that there are several spNadE homologs that have their structure experimentally determined. Homologous NAD+ synthetases that had the highest sequence identity originated from S. typhimurium (PDB code: 3HMQ, 68 % sequence identity; stNadE), E. coli (PDB code: 1WXI, 65% sequence identity; ecNadE), B. anthracis (PDB code: 2PZA; 58% sequence identity; baNadE) and B. subtilis (PDB code: 2NSY; 57% sequence identity; bsNadE). The structure of these proteins were used to identify the putative substrate binding sites for spNadE, and gave the following RMSD values, using Coot SSM superpose: 0.7 Å (over 251 C atoms) for stNadE; 0.6 Å (over 257 C atoms) for ecNadE, 0.7 Å (over 254 C atoms) for baNadE, and 0.9 Å (over 254 C atoms) for bsNadE [22]. Sublingual NMN

spNadE Active Site – Sequence similarity analysis in combination with structural studies of structural homologs bsNadE and ecNadE, indicates that there are approximately 18 residues responsible for the architecture of the active site. The closed conformation of the active site loop observed in structure of bsNadE (PDB code: 1EE1) is not present in the spNadE structures reported here. This result is possibly due to high entropy in that region. Through sequence similarity studies of this region, specifically residues 215-223, it was determined that these residues are highly conserved and make up a loop structure within that region. The loop was modeled using the structure of a homolog – bsNadE (PDB code: 1EE1) as a template (Fig. 6). It should be noted that the bsNadE (PDB code: 1EE1) structure was one of the few structures that determined the orientation for the loop region [23]. This loop has also been indicated in the stabilization of Mg2+ within the ATP binding site, as the ATP binding site shares three residues with this site. For spNadE, the residues of the loop of interest include (corresponding bsNadE residues are in bold): E215 (L204), K216 (K205), V217 (E206), P218 (P207), T219 (T208), A220 (A209), D221 (D210), L222 (L211), E223 (L212). Both loops have approximately 67% sequence identity. Unfortunately, numerous attempts to co-crystallize spNadE

with ATP, NaAD, and/or NAD+, with and without Mg2+, were unsuccessful.
spNadE ATP/ Mg2+ Binding – ATP and Mg2+ binding sites in spNadE were shown to be

composed of residues from a single protein chain. Moreover, structural analysis indicates that the binding of ATP occurs solely within the individual chains of the dimeric assembly and not at the interface. Residues involved in the conserved “SGGXD” motif (residues S56-D60) are also found at this site.

Sequence similarity studies of spNadE, using homologs from ecNadE (PDB code: 1WXI) and bsNadE (PDB code: 1EE1), identified residues: L53, G54, I55, S56, D60, S61, V89, R90, L91, R150, T168, K197, V217, P218, and T219 to be responsible for providing a binding pocket for ATP. Residues P218 and T219 (as well as any other residues between 216-227) are not visible in the electron density due to conformational flexibility in that region.

Dr. Oz likes Meratrim for Safe Weight Loss

Meratrim is getting a lot of publicity these days with new studies showing it works in conjunction with healthy eating and exercise to shave away the pounds. Recent publicity from a featured presence on “The Dr. Oz Show” has sparked a lot of interest in the weight loss supplement that features ingredients like Garcinia Mangostana and Sphaeranthus indicus. They appear to help block fat storage, which accounts for a lot of extra pounds.

Direct Digital, LLC has created Meratrim as part of its Slim Science line that also features Slim Science Thermogenic appetite suppressant. This cutting-edge nutritional health and weight loss supplement has been tested and found helpful in connection with maintaing healthy activity and good eating to take off the weight.

Bodies store more fat than they need for energy. It’s a genetic response to thousands of years of human activity. Fat storage has evolved to such an extent that it stands in the way of weight loss. The supplement’s main ingredients Garcinia Mangostana and Sphaeranthus indicus have been shown to help promote fat burning in clinical testing.

Testing included double-blind trials with half the participants given placebos. Test results showed reduced waists and hops along with weight loss over a 90-day period. Dr. Oz offered a plan with work with the supplement to lose weight, He called for a 400 milligram tablet 30 minutes before breakfast and another 30 minutes before dinner.

Dr. Oz Test participants kept calories consumption under 2,000 calories a day while exercising for 30 minutes, five days a week. They found they started to lose weight in two weeks and lost about a pound a week at minimum.

Meratrim fruit and flower slimming formula is recommended for any overweight adult over 18 years old. Results vary. It’s a proprietary blend that works better than ingredients used in generic form and by themselves or in other combinations. Sphaeranthus indicus is a flower extract while Garcinia Mangostan is a fruit rind extract. The have been shown to influence fat metabolism burning processes.

All ingredients in the proprietary blend are plant-based, so no problem for vegetarians. It doesn’t contain caffeine, other stimulants or artificial flavors. It’s recommended safe for adults over age 50. The brand is trademarked, so only trust the real deal from InterHealth. Approved brands include Re-Body Fruit and Flower Slimming Formula, Prosource’s Zycor, Xango’s FAVAO, NV Clinical, and Life Extension’s Advanced Anti-Adipcyte Formula.

My Experience with New Life Botanical Garcinia Cambogia

newlifebotanical-garciniaWhen I first heard about this supposed new miracle weight loss wonder, I immediately ordered a bottle. I can say I didn’t get my hopes up much since nothing really worked in the past, but I’d be lying. I think anyone who orders diet pills then says they never had their hopes up knows that deep down they did – or they wouldn’t have bought it. Right?

After two weeks though, I hadn’t seen much change. After almost a month, I still had only lost about four pounds. Honestly? I could have probably done that on my own with a little exercise. So I called to find out how I could get my refund. This is when I found out that you could only return unopened packages. What? Yep. Boy I was furious.

Then I started to do a little research and low and behold, that’s when I found AlivebyNature (who sells New Life Botanical Garcinia). Come to find out that they had reviewed the particular brand I had bought (I won’t mention any names here) and had warned about buying from this company. Apparently, it didn’t even have enough of the magical ingredient (HCA) to be effective. Alive had so much helpful information on their site and was kind enough to promptly reply to my questions, so deciding to give it one more shot, I ordered from them.

This time things were different. The first thing I noticed when I started taking it is that my cravings seem to disappear. I knew that it was supposed to help with suppressing your hunger, but I wasn’t aware of how effective it would be to taking away cravings that I’ve seemingly been cursed with. This is probably one of the biggest reasons I’ve struggled for so long to lose weight. I can just about assume that this is the case with many others, too.

After a few weeks, I was feeling really good about myself. My tight jeans were getting much more comfortable and my comfortable jeans almost required a belt. So I figured it was time to hit the scale. Two pounds? How could my clothes be fitting so much different if I had only lost two pounds? Again, I contacted them.

Their answer made complete sense after explaining it. It’s simple, really. Even if the scale isn’t saying much, that’s OK. Garcinia burns FAT. So you could lose fat, but build and strengthen muscle without the scale ever moving much. BUT you look leaner and your body is reshaping itself due to the amount of fat that’s disappearing.

So I kept taking it until it was gone. That entire month, I lost nine pounds. It may not sound like much, but it is. I wasn’t doing much of anything differently, though I did try to walk down to the park for a break during lunch when I could… that’s about it. So I was impressed and ordered another two bottles. I’m now on month three and so far have lost a total of 16 pounds, have dropped 3 dress sizes and am about to reach my goal.

So overall I have to agree with what people are saying. This stuff works. But you have to be careful about which product you buy and who you buy it from.

Tackle Diet, Exercise Together for Best Results?

exercise and dietIf you have to choose one at a time, hit the gym first, researchers add

If you’re trying to get healthy, tackling both diet and exercise is better than trying to improve one lifestyle habit at a time, new research suggests.

The researchers did add that if you need to start with just one lifestyle change, choose exercise. They found that changing diet first may interfere with attempts to establish a regular exercise routine.

The study included 200 people, aged 45 and older, who were inactive and had poor diets. They were split into four groups: new diet and exercise habits at the same time; diet changes first and starting exercise a few months later; starting exercise first and making diet changes a few months later; and no diet or exercise changes.

The groups received telephone coaching and were tracked for a year. Those who made diet and exercise changes at the same time were most likely to meet U.S. guidelines for exercise (150 minutes per week) and nutrition (5 to 9 servings of fruit and vegetables per day), and to keep calories from saturated fat at less than 10 percent of their total intake of calories.

The people who started with exercise first and diet changes a few months later also did a good job of meeting both the exercise and diet goals, but not quite as good as those who made exercise and diet changes at the same time, the Stanford University School of Medicine researchers said in a news release from Stanford.

The participants who made diet changes first and started exercise later did a good job of meeting the dietary goals but didn’t meet their exercise targets. This may be because each type of change has unique characteristics, explained study author Abby King, a professor of health research and policy and of medicine.

“With dietary habits, you have no choice; you have to eat. You don’t have to find extra time to eat because it’s already in your schedule. So the focus is more on substituting the right kinds of food to eat,” she said in the news release.

However, people with busy schedules may have difficulty finding time for exercise. King noted that even the people in the most successful group (diet and exercise changes at the same time) initially had trouble meeting their exercise goal, but did achieve it by the end of the study.

The study was published online April 21 in the journal Annals of Behavioral Medicine.

6 delicious ways to snack on superfood chia

172413_Green Bags_KDM_By now, you’ve heard about chia as the hot new healthy ingredient. But you probably have no idea what do with it. You aren’t alone. For many of us, our experience with chia is limited to Chia Pets, those kitschy animal-shaped lawn ornaments that were popular several years ago. But when eaten, chia seeds are a nutritional no-brainer, loaded with omega-3 fatty acids. And since they can be eaten raw, they’re an easy way to up the health factor of just about any meal.

Chia is an ancient seed that dates back to the Aztecs, who used it as a source of energy and endurance. The word chia is used to describe two plants, salvia hispanica and salvia columbariae and is mainly grown in Central and South America. It can be eaten whole or ground up and added to baked goods and other products. As interest in the health benefits of chia grows, various food brands have been adding chia to their products. Here, some tasty ways to add a little chia to your diet.

New York Superfoods Chia Peanut Butter

On its own, natural peanut butter is a great source of protein, but add some chia seeds to it and you’ve got a snack loaded with fiber and omega-3s—perfect for a before work out bite. New York Superfood’s version of chia peanut butters are free of preservatives and hydrogenated oils and come in six unique flavors such as Manhattan Mud (blended with vegan dark chocolate) Tribeccah Nectar (with agave nectar) and Boulder Heat (with paprika).

Salba Smart Tortilla Chips and Boost packets

Salba chia is a trademarked version of chia grown in Peru under strictly controlled conditions to ensure nutritional consistency. Salba Smart is a line of organic snack foods that contain this form of chia. Their tortilla chips, available in white, blue and yellow corn, are especially tasty, and the company recently launched Boost packets, a 0.5-ounce serving of Salba seeds, that can be sprinkled onto yogurt, cereal or into smoothies.

Nature’s Path Chia Plus Frozen Waffles

Try these organic breakfast waffles, packed with chia seeds, quinoa and amaranth. They’re also gluten free!

Mamma Chia Vitality Beverages

These delicious organic drinks—the first chia-based beverage on the market—are gluten free and full of protein, calcium, and omega-3 fatty acids. The consistency reminded me of aloe drinks (I am thinking about freezing them into ice pops for my one-year-old!) Sweetened with agave nectar, the drinks are available in nine flavors including Blackberry Hibiscus, Cherry Lime and Pomegranate Mint. Plus, Mamma Chia donates one percent of their gross sales to farmers and community groups that build healthy local food systems.

KIND Healthy Grains Maple Walnut Clusters with Chia & Quinoa While I’m a fan of making my own granola, KIND’s version is a worthy splurge. Loaded with 300mg of omega-3 fatty acids and 17g of whole grains per serving, breakfast doesn’t get much healthier. Oh and it tastes pretty good too!

Happy Family Happy Tot Pouches

These squeezable, organic fruit and vegetable packets contain Salba chia, and are a great way to get this ancient grain into your baby or toddler’s diet! Available in six flavor combinations.

Pure Garcinia Cambogia Helps You Lose Weight


Garcinia Cambogia extract is the newest of the natural weight loss programs that we can confidently recommend. Again, a Dr. Oz featured product. This one is a triple-fat-burning-threat! It blocks fat. It melts fat you already have. It curbs your appetite.

We’ve reviewed dozens of the top brands ourselves, and so far, the winner is NewLifeBotanicals, chosen #1 by the Diet Management Association of America ( It is available at select Whole Foods and GNC stores, or a reputable store such as Alivebynature.



The reason the Pure Garcinia Cambogia is so popular is because it’s a cheap herbal supplement available on the market. The fruit makes you feel full, so you don’t feel like eating anymore. It started in Malaysia as a soup, but it has become popular in many different places around the world. The fruit is sometimes called tamarind, and it’s native to Indonesia. You can now find the fruit in West/Central African, Southeast Asia and India.

You can also find Garcinia Cambogia in South Asian cuisine such as chutneys and curries, and its good for curing fruit and preservation. The fruit is often shapes like a fruit, and its small in size. Consumers like to eat the fruit because it makes them feel full as it will block your appetite. The plant should be eaten 30 minutes before every major meak.

The drug has HCA in it; that’s the short name for hydroxycitric acid. You can double or triple your weight loss when you eat the fruit. HCA ia natural extract, and it works best with diet and exericse. As long as you eat right and get plenty of exercise, you will probably lose around four pounds per month. This is a good food for people who are emotional eaters because it will increase your serotonin levels.

This increase will put you in a better mood, and it will help you sleep better at night. HCA extract is usefull because it will help you with your apptite, and it will assist you with blocking fats. The main ingredient that stops you from making fats is the carbohydrate names citrate lyase. If it’s not immediately stored, the carb is turned into fats. HCA can be used to stop the production of LDL and triglycerides. HCA is also useful for increasing serotonin levels, and this can help you feel full. There are no known side effects to the fruit, so it’s a safe way to lose weight.

These are just some of the ways that Garcinia Cambogia can assist you with your weight loss goals. Good luck with your weight loss program!

Weight Loss with the Green Coffee Bean Extract

lost-weightA few people that come to mind may have something in common with the people he or she knows. For example, there are more people that qualify in the weight loss category than ever before. From what he or she knows, the weight that people have been carrying around for years did not came to exist until the 1990.

The Green coffee bean extract has been well known to help people lose more weight than without it because the caffeine helped speed up the weight loss process. This Green coffee bean extract worked so well that people are amazed with what he or she get. When using a product that has the fat burning ingredient in conjunction to what he or she eat or drink, that will quickly help get rid of the fat. However, it is still necessary to eat nutritious food and exercise on a daily basis to make it even more effective.

Doctor Oz recommended this diet due to the side effects that it bring to he and she who wanted to lose weight but drink coffee at the same time. For example, most people like coffee which makes perfect sense. Second reason is with caffeine that’s included, it will give energy to the ones who do drink it.

Due to the popularity of this diet, he or she will feel and see the effect of using it. One other side effects of using this product is that it is addicting which this coffee is not like all the other kinds that are out there sold in stores. It is so different which is why the green coffee bean extract product is popular all over the world. Since there are more people that are coffee drinkers than anything, what he or she gets out of it is not only worth it but can drink it anytime he or she wants.

There is a good reason why Doctor Oz recommended it which is to help people lose weight and drink something that most people like drinking. It can be used as a morning coffee which is what he or she does as well as a lunch beverage as well. No matter what time and day it is, this product can be used as a beverage 24 7.

Raspberry Not Really Ultra Drops

Raspberry ultra drops are part of a weight loss plan. It is advertised on the Internet the same way that any fraud scheme and scam is marketed. It tries to appear to be the perfect weight loss plan that will cause everyone to loss one to two pounds per day. They will buy the product and incorporate it into their daily and will never worry about losing weight again. Unfortunately, this is not correct.

These Raspberry ultra drops have something called raspberry ketone in them. Supposedly, they have fat burning properties and lots of anti-oxidants in them. What is not mentioned is that teas have lots of anti-oxidants have in them. Many fat burners do not work on certain people. Everyone will not have success with raspberry ketone.

Scam and fraud on the Internet is often done by marketing products that are not effective. Unfortunately, many people who purchased this ketone diet have seen limited or no results. A few of the users of it have seen results but were not aware how quickly the results would go away. This is why the BBB and many websites have reports of unhappy customers who wanted to report that the product is not legitimate and makes false claims.

A ketone supplement may help people to lose weight. However, it will now keep weight off of them. A good exercise plan and a balanced diet will still be necessary. A fat burning diet from a capsule has very limited results. It will get rid of fat but people will become very hungry. They may see results but they are only temporary because the people are still hungry and their body will stop burning the fat as soon as they stop taking the capsules. If they do not exercise, their metabolism will slow down and small amounts of food will be stored in the body and cause them to gain the weight again almost immediately.

The biggest false claim about this Raspberry product is that it is 500 times stronger than the capsules of other companies. This information is biased and it is based off of unknown information. Everyone who uses these capsules does not report results. Some people use them to lose a pound or two while others want to lose a hundred pounds. People vary in age, sex, genetics and metabolism speed. This is why it would be impossible to know which capsule is the best.

Weight Loss: Yacon Extract Proven to Work

Yacon Products Offer Weight Loss Success

Yacon is one of the most promising weight loss supplements to emerge on the market. Various studies have found that it both promoted weight loss, and even the television medical expert Dr. Oz has featured it on his show with a panel of experts. Ever since the Dr. Oz episode, it has rivaled garcinia cambogia as one of the best weight loss supplements because it is healthy, filling, and all natural.

This vegetable can be found in a variety of different forms. One of the most common is a syrup, which the dieter takes a swallow of with each meal three times a day. It can also be taken as a powder. Both come from the yacon plant of Andean South America, which has been a popular part of the diet there since Incan times. It is a potato-like vegetable high in fiber, so it is very filling, and also low in calories, making it an easy addition to any diet. Plus, since yacon supplements has a low glycemic index, so it breaks down slowly and has less affect upon the blood sugar.

Many products reach the market as an all-natural weight loss secret, but this yacon syrup actually does have some solid research backing its claims. For one, there was a 120-day, double-blind placebo study which found significant weight loss among obese patients taking the supplement. Dr. Oz also tested out this vegetable and syrup with a group of sixty women and the results of his study show tremendous promise as well. Forty women completed the project and lost an average of 2.9 pounds. Fourteen lost more than five pounds. These results are a sign of how well the syrup can assist in sustainable, healthy weight loss.

Yacon syrup and power work with the probiotic bacteria which live in the gut. It contains Fructooligosaccharide, or FOS, which tastes sweet but is processed in the body more slowly than sugar and causes that regulation of blood sugar. The high concentration of fiber leaves people feeling fuller longer and according to Dr. Oz, it also reduces the hunger hormones and suppresses the appetite so people can eat less without feeling as hungry afterwards.

This wonderful weight loss product works just as well as garcinia cambogia at promoting weight loss, and it does so in a natural manner with few side effects. Its tremendous promise is matched by results, and supported by medical experts.